Differential effects of methylmercury on the synthesis of protein species in dorsal root ganglia of the rat

International Nuclear Information System (INIS)

Kasama, Hidetaka; Itoh, Kazuo; Omata, Saburo; Sugano, Hiroshi

1989-01-01

Dorsal root ganglia from control and methylmercury(MeHg)-treated rats were incubated in vitro with 35 S-methionine and the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3 H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions. (orig.)

eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root Ganglion Neurons

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Jamie K. Moy

2018-02-01

Full Text Available Plasticity in dorsal root ganglion (DRG neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5′ cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4ES209A and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4ES209A mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming.

Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus.

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Zhang, Tie-Yuan; Keown, Christopher L; Wen, Xianglan; Li, Junhao; Vousden, Dulcie A; Anacker, Christoph; Bhattacharyya, Urvashi; Ryan, Richard; Diorio, Josie; O'Toole, Nicholas; Lerch, Jason P; Mukamel, Eran A; Meaney, Michael J

2018-01-19

Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide transcriptional and methylation differences between dorsal and ventral DG, including at key developmental transcriptional factors. Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression. Enrichment also enhances dorsal-ventral differences in DNA methylation, including at binding sites of the transcription factor NeuroD1, a regulator of adult neurogenesis. These results indicate a dorsal-ventral asymmetry in transcription and methylation that parallels well-known functional and anatomical differences, and that may be enhanced by environmental enrichment.

Modified dorsal root entry zone lesioning for intractable pain relief in patients with root avulsion injury.

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Takai, Keisuke; Taniguchi, Makoto

2017-08-01

OBJECTIVE Dorsal root entry zone (DREZ) lesioning has been the most effective surgical treatment for the relief of intractable pain due to root avulsion injury, but residual pain and a decrease in pain relief in the follow-up period have been reported in 23%-70% of patients. Based on pain topography in the most recent studies on neuropathic pain, the authors modified the conventional DREZ lesioning procedure to improve clinical outcomes. The presumed rationale for this procedure is to eliminate the spontaneous discharges of neurons in the superficial spinal dorsal horn as well as wide dynamic range neurons in the deep spinal dorsal horn. METHODS Ten patients with avulsion-related pain underwent surgery between 2011 and 2015. The surgical procedure was described and postoperative pain relief was assessed as follows: excellent (residual pain never exceeded 3 on the visual analog scale [VAS] without medication), good (residual pain never exceeded 5 on the VAS with medication), and poor (residual pain was greater than 5 with medication). Specific perioperative complications were assessed. RESULTS The aim of this surgical procedure was to destroy the deeper layers of the posterior horn of spinal gray matter, which was in contrast to the procedures of Nashold and Sindou, which were to destroy the superficial layers. All patients achieved excellent (n = 7, pain relief without medication) or good (n = 3, pain relief with medication) pain relief postoperatively, and the recurrence of pain was not reported in any patients (median 29 months after surgery, range 12-64 months). Nine patients (90%) achieved complete pain relief (a score of 0 or 1 on the VAS) with or without medication. No surgical site complications such as infection or CSF leakage were noted. No motor deficit was observed in any patient. A sensory deficit was observed in 2 patients and disappeared within 1 month in 1 patient. New pain at the adjacent level of DREZ lesioning was observed in 3 patients and

Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

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Benitez, Suzana U.; Barbizan, Roberta; Spejo, Aline B.; Ferreira, Rui S.; Barraviera, Benedito; Góes, Alfredo M.; de Oliveira, Alexandre L. R.

2014-01-01

Root lesions may affect both dorsal and ventral roots. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. The loss of such sensorial input directly disturbs the spinal circuits thus affecting the functionality of the injuried limb. The present study evaluated the motor and sensory improvement following dorsal root reimplantation with fibrin sealant (FS) plus bone marrow mononuclear cells (MC) after dorsal rhizotomy. MC were used to enhance the repair process. We also analyzed changes in the glial response and synaptic circuits within the spinal cord. Female Lewis rats (6–8 weeks old) were divided in three groups: rhizotomy (RZ group), rhizotomy repaired with FS (RZ+FS group) and rhizotomy repaired with FS and MC (RZ+FS+MC group). The behavioral tests electronic von-Frey and Walking track test were carried out. For immunohistochemistry we used markers to detect different synapse profiles as well as glial reaction. The behavioral results showed a significant decrease in sensory and motor function after lesion. The reimplantation decreased glial reaction and improved synaptic plasticity of afferent inputs. Cell therapy further enhanced the rewiring process. In addition, both reimplanted groups presented twice as much motor control compared to the non-treated group. In conclusion, the reimplantation with FS and MC is efficient and may be considered an approach to improve sensory-motor recovery following dorsal rhizotomy. PMID:25249946

Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells.

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Zhang, Meixiang; Ngo, Justine; Pirozzi, Filomena; Sun, Ying-Pu; Wynshaw-Boris, Anthony

2018-03-15

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages. Here, we present three protocols that are highly efficient in differentiating mouse and human ESCs, as well as human iPSCs, into a homogeneous and stable population of dorsal NPCs. These protocols will be useful for modeling cerebral cortical neurological and neurodegenerative disorders in both mouse and human as well as for high-throughput drug screening for therapeutic development. We optimized three different strategies for generating dorsal telencephalic NPCs from mouse and human pluripotent cell types through single or double inhibition of bone morphogenetic protein (BMP) and/or SMAD pathways. Mouse and human pluripotent cells were aggregated to form embryoid bodies in suspension and were treated with dorsomorphin alone (BMP inhibition) or combined with SB431542 (double BMP/SMAD inhibition) during neural induction. Neural rosettes were then selected from plated embryoid bodies to purify the population of dorsal NPCs. We tested the expression of key dorsal NPC markers as well as nonectodermal markers to confirm the efficiency of our three methods in comparison to published and commercial protocols. Single and double inhibition of BMP and/or SMAD during neural induction led to the efficient differentiation of dorsal NPCs, based on the high percentage of PAX6-positive cells and the NPC gene expression profile. There were no statistically

Upregulation of miR-375 level ameliorates morphine analgesic tolerance in mouse dorsal root ganglia by inhibiting the JAK2/STAT3 pathway

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Li HQ

2017-05-01

Full Text Available Haiqin Li, Rong Tao, Jing Wang, Lingjie Xia Department of Clinical Pain, The People’s Hospital of Henan Province, Zhengzhou, People’s Republic of China Abstract: Several lines of evidence indicate that microRNAs (miRNAs modulate tolerance to the analgesic effects of morphine via regulation of pain-related genes, making dysregulation of miRNA levels a clinical target for controlling opioid tolerance. However, the precise mechanisms by which miRNAs regulate opioid tolerance are unclear. In the present study, we noted that the miR-375 level was downregulated but the expression of Janus kinase 2 (JAK2 was upregulated in mouse dorsal root ganglia (DRG following chronic morphine treatment. The miR-375 levels and JAK2 expression were correlated with the progression of morphine tolerance, and upregulation of miR-375 level could significantly hinder morphine tolerance. This was ameliorated by JAK2 knockdown. Prolonged morphine exposure induced the expression of brain-derived neurotrophic factor (BDNF in a time-dependent manner in the DRG. This was regulated by the miR-375 and JAK2–signal transducer and activator of transcription 3 (STAT3 pathway, and inhibition of this pathway decreased BDNF production, and thus, attenuated morphine tolerance. More importantly, we found that miR-375 could target JAK2 and increase BDNF expression in a JAK2/STAT3 pathway-dependent manner. Keywords: morphine tolerance, miR-375, JAK2, BDNF

Homeobox gene expression in adult dorsal root ganglia: Is regeneration a recapitulation of development?

NARCIS (Netherlands)

Vogelaar, C.F.

2003-01-01

Neurons of the peripheral nervous system are able to regenerate their peripheral axons after injury, leading to complete recovery of sensory and motor function. The sciatic nerve crush model is frequently used to study peripheral nerve regeneration. Sensory neurons in the dorsal root ganglia (DRGs)

Morphological evaluation of lumbar dorsal root ganglion on three-dimensional magnetic resonance imaging

International Nuclear Information System (INIS)

Shen Jun; Chen Jianyu; Zhou Cuiping; Liang Biling; Xu Xiaomao

2007-01-01

Objective: To investigate the morphological features of normal lumbar dorsal root ganglia using a three-dimensional (3D) coronal MR imaging. Methods: One hundred and fifteen volunteers were included. Ages ranged from 15 to 75 years, with a mean of 40 years. Coronal 3D fast field echo (FFE) with water selective excitation (Proset) MR examination of 1150 dorsal root ganglia were underwent at nerve root levels from L1 to L5. The source coronal images were further reconstructed into a series of rotational alignment coronal images with an interval angel of 12 degree using maximum intensity projection (MIP) technique. All DRGs of bilateral spinal nerve from L1 to L5 were morphologically analyzed on the original and MIP images including qualitative evaluation of the location, signal intensity, architecture and quantitative dimensional measurement. Results: There were 225, 225, 219, 210 and 160 foraminal ganglia from L1 to L5 level, respectively. The incidence of intraspinal ganglia from L3 to L5 gradually increased with a maximum at L5 level of 29.1% (X 2 =188.371, P<0.01). One thousand one hundred and thirteen (96.8%) DRGs were intermediate intensity on MIP images. The width and length of L1 DRGs were from 2. 00 to 5.50 mm (3.38±0.77) mm, 2.00 to 7.00 mm (4.35±0.89) mm, respectively. The width and length of L5 DRGs were from 3.50 to 9.00 mm (6.40±0.91) mm, 6.00 to 19.00 mm [(11.58± 2.25) mm], respectively. There was statistically significant difference in the dimension of DRGs from L5 to L1 (F=41.527-205.998, P<0.01). In 1150 DRGs, three types of architecture of DRGs including 822 singular, 317 bi- and 11 tri-ganglion DRGs could be found with a high prevalence of the bi-ganglia in L4 and L3 DRGs and a higher incidence of the singular ganglia in the L5 and L2 and L1 DRGs. Conclusions: The normal anatomy and variant of the lumbar dorsal root ganglia could be clearly demonstrated by 3D FFE MR imaging with Proset. As the level of the nerve root traveled down caudally

Inflammatory mediators potentiate high affinity GABA(A) currents in rat dorsal root ganglion neurons.

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Lee, Kwan Yeop; Gold, Michael S

2012-06-19

Following acute tissue injury action potentials may be initiated in afferent processes terminating in the dorsal horn of the spinal cord that are propagated back out to the periphery, a process referred to as a dorsal root reflex (DRR). The DRR is dependent on the activation of GABA(A) receptors. The prevailing hypothesis is that DRR is due to a depolarizing shift in the chloride equilibrium potential (E(Cl)) following an injury-induced activation of the Na(+)-K(+)-Cl(-)-cotransporter. Because inflammatory mediators (IM), such as prostaglandin E(2) are also released in the spinal cord following tissue injury, as well as evidence that E(Cl) is already depolarized in primary afferents, an alternative hypothesis is that an IM-induced increase in GABA(A) receptor mediated current (I(GABA)) could underlie the injury-induced increase in DRR. To test this hypothesis, we explored the impact of IM (prostaglandin E(2) (1 μM), bradykinin (10 μM), and histamine (1 μM)) on I(GABA) in dissociated rat dorsal root ganglion (DRG) neurons with standard whole cell patch clamp techniques. IM potentiated I(GABA) in a subpopulation of medium to large diameter capsaicin insensitive DRG neurons. This effect was dependent on the concentration of GABA, manifest only at low concentrations (emergence of injury-induced DRR. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

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Vandewauw Ine

2013-02-01

Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

MRI of enlarged dorsal ganglia, lumbar nerve roots, and cranial nerves in polyradiculoneuropathies

International Nuclear Information System (INIS)

Castillo, M.; Mukherji, S.K.

1996-01-01

This paper describes the MRI findings in four patients with a clinical diagnosis of hypertrophic polyradiculoneuropathies. In two examination of the lumbar spine showed enlarged nerve roots and dorsal ganglia, and similar findings were present in the cervical spine in a third. The cisternal portions of the cranial nerves were enlarged in another patient. MRI allows identification of enlarged nerves in hypertrophic polyradiculopathies. (orig.)

Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.

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Matsushita, Yumi; Manabe, Miki; Kitamura, Naoki; Shibuya, Izumi

2018-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

Suramin affects capsaicin responses and capsaicin-noxious heat interactions in rat dorsal root ganglia neurones

Czech Academy of Sciences Publication Activity Database

Vlachová, Viktorie; Lyfenko, Alla; Vyklický st., Ladislav; Orkand, R. K.

2002-01-01

Roč. 51, č. 2 (2002), s. 193-198 ISSN 0862-8408 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : dorsal root ganglia neurones * vanilloid receptor * capsaicin-noxious heat Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

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Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

1996-09-01

To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

Avaliação da hiperalgesia e alterações histológicas do gânglio da raiz dorsal induzidas pelo núcleo pulposo Evaluation of hyperalgesia and histological changes of dorsal root ganglion induced by nucleus pulposus

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André Luiz de Souza Grava

2010-01-01

estruturas do gânglio da raiz dorsal e apresentaram aumento da intensidade nos períodos mais longos de observação.OBJECTIVE: To evaluate hyperalgesia and histological changes of dorsal root ganglia induced by nucleus pulposus (NP contact. METHODS: Twenty Wistar rats were used, divided into two experimental groups. In one of the groups, a fragment of the autologous NP was removed from the sacroccocigeal region and deposited on the L5 dorsal root ganglia. In the control group, the NP was removed from the sacrococcygeal region, L5 dorsal root ganglia were exposed and covered by a piece of adipous fat tissue. Hyperalgesia was evaluated by the von Frey electronic test and Hargreaves test, and histological changes of the dorsal root ganglia by HE staining and immunohistochemistry using iNOS. The evaluation of hyperalgesia and histological changes of the dorsal root ganglia were performed on the third postoperative day and after 1, 3, 5, and 7 weeks. RESULTS: NP induced higher intensity mechanical and thermal hyperalgesia. Dorsal root ganglia in contact with nucleus pulposus presented histological changes and the intensity of these changes were proportional to the length of time in contact. The expression of iNOS was higher in the glial cells in contact with the nucleus pulposus. CONCLUSION: The contact of nucleus pulposus with dorsal root ganglia induced histological changes and mechanical and thermal hyperalgesia. These changes were more intense after longer period of evaluation.

Transient Sensory Recovery in Stroke Patients After Pulsed Radiofrequency Electrical Stimulation on Dorsal Root Ganglia: A Case Series.

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Apiliogullari, Seza; Gezer, Ilknur A; Levendoglu, Funda

2017-01-01

The integrity of the somatosensory system is important for motor recovery and neuroplasticity after strokes. Peripheral stimulation or central stimulation in patients with central nervous system lesions can be an effective modality in improving function and in facilitating neuroplasticity. We present 2 hemiplegic cases with sensory motor deficit and the result of the pulsed radiofrequency (PRF) electrical stimulation to the dorsal root ganglia. After PRF electrical stimulation, significant improvement was achieved in the examination of patients with superficial and deep sensation. However, during the follow-up visits were observed that the effect of PRF electrical stimulation disappeared. We believe that these preliminary results could be used in the development of future prospective cohort studies and randomized controlled trials that focus on the effect of PRF electrical stimulation on dorsal root ganglia to treat sensory deficits in poststroke patients.

Advanced type 1 diabetes is associated with ASIC alterations in mouse lower thoracic dorsal root ganglia neurons.

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Radu, Beatrice Mihaela; Dumitrescu, Diana Ionela; Marin, Adela; Banciu, Daniel Dumitru; Iancu, Adina Daniela; Selescu, Tudor; Radu, Mihai

2014-01-01

Acid-sensing ion channels (ASICs) from dorsal root ganglia (DRG) neurons are proton sensors during ischemia and inflammation. Little is known about their role in type 1 diabetes (T1D). Our study was focused on ASICs alterations determined by advanced T1D status. Primary neuronal cultures were obtained from lower (T9-T12) thoracic DRG neurons from Balb/c and TCR-HA(+/-)/Ins-HA(+/-) diabetic male mice (16 weeks of age). Patch-clamp recordings indicate a change in the number of small DRG neurons presenting different ASIC-type currents. Multiple molecular sites of ASICs are distinctly affected in T1D, probably due to particular steric constraints for glycans accessibility to the active site: (i) ASIC1 current inactivates faster, while ASIC2 is slower; (ii) PcTx1 partly reverts diabetes effects against ASIC1- and ASIC2-inactivations; (iii) APETx2 maintains unaltered potency against ASIC3 current amplitude, but slows ASIC3 inactivation. Immunofluorescence indicates opposite regulation of different ASIC transcripts while qRT-PCR shows that ASIC mRNA ranking (ASIC2 > ASIC1 > ASIC3) remains unaltered. In conclusion, our study has identified biochemical and biophysical ASIC changes in lower thoracic DRG neurons due to advanced T1D. As hypoalgesia is present in advanced T1D, ASICs alterations might be the cause or the consequence of diabetic insensate neuropathy.

The effect of collagenase on nerve conduction velocity of dorsal root ganglion in rats

International Nuclear Information System (INIS)

Zhuang Wenquan; Li Heping; Yang Jianyong; Chen Wei; Huang Yonghui; Guo Wenbo

2006-01-01

Objective: To study the functional effects of collagenase on dorsal root ganglion (DRG) in rats by evoked potential conduction velocity measurement. Methods: A total of 57 male healthy Sprague-Dawley rats were randomized into 7 groups: normal group, acute collagenase group, subacute collagenase group, chronic collagenase group, acute pseudo-operation group, subacute pseudo-operation group, chronic pseudo-operation group. 1200 units of collagenase was reconstituted in 4 ml isotonic saline prior for the experimental application. The left fifth lumbar DRG was exposed in each rat and followed by 1 ml collagenase solution (300 units) dropping on the exposed DRG in collagenase groups; and similarly 1 ml isotonic saline was applied to each of the exposed DRG in pseudo-operation groups. the effects of collagenase on nerve conduction velocity (NCV) were analyzed 1 hour, 1 week or 1 month after the procedure. The statistical analysis was carried out by software SPSS11.0. Results: The differences of NCV measured by evoked potential method between all groups including the normal group, collagenase groups, and pseudo-operation groups were not significant (P>0.05). Conclusion: The Neuroelectricity physiologic function of dorsal root ganglion and nerve would not be damaged by collagenase used in therapeutic concentration. (authors)

No further loss of dorsal root ganglion cells after axotomy in p75 neurotrophin receptor knockout mice

DEFF Research Database (Denmark)

Sørensen, B.; Lamm, Trine Tandrup; Koltzenburg, M.

2003-01-01

The role of the p75 neurotrophin receptor for neuronal survival after nerve crush was studied in L5 dorsal root ganglia (DRG) of knockout mice and controls with assumption-free stereological methods. Numbers of neuronal A- and B-cells were obtained using the optical fractionator and optical...

Orexin A and Orexin Receptor 1 axonal traffic in dorsal roots at the CNS/PNS interface

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Damien eColas

2014-02-01

Full Text Available Hypothalamic orexin/hypocretin neurons send long axonal projections through the dorsal spinal cord in lamina I-II of the dorsal horn at the interface with the peripheral nervous system (PNS. We show that in the dorsal horn OXA fibers colocalize with substance P (SP positive afferents of dorsal root ganglia (DRG neurons known to mediate sensory processing. Further, OR1 is expressed in p75NTR and SP positive DRG neurons, suggesting a potential signaling pathway between orexin and DRG neurons. Interestingly, DRG sensory neurons have a distinctive bifurcating axon where one branch innervates the periphery and the other one the spinal cord (pseudo-unipolar neurons, allowing for potential functional coupling of distinct targets. We observe that OR1 is transported selectively from DRG toward the spinal cord, while OXA is accumulated retrogradely toward the DRG. We hence report a rare situation of asymmetrical neuropeptide receptor distribution between axons projected by a single neuron. This molecular and cellular data are consistent with the role of OXA/OR1 in sensory processing, including DRG neuronal modulation, and support the potential existence of an OX/HCRT circuit between CNS and PNS.

Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni

OpenAIRE

Partata,W.A.; Krepsky,A.M.R.; Marques,M.; Achaval,M.

1999-01-01

Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spina...

Intracellular responses to frequency modulated tones in the dorsal cortex of the mouse inferior colliculus

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Ruediger eGeis

2013-01-01

Full Text Available Frequency modulations occur in many natural sounds, including vocalizations. The neuronal response to frequency modulated (FM stimuli has been studied extensively in different brain areas, with an emphasis on the auditory cortex and the central nucleus of the inferior colliculus. Here, we measured the responses to FM sweeps in whole-cell recordings from neurons in the dorsal cortex of the mouse inferior colliculus. Both up- and downward logarithmic FM sweeps were presented at two different speeds to both the ipsi- and the contralateral ear. Based on the number of action potentials that were fired, between 10-24% of cells were selective for rate or direction of the FM sweeps. A somewhat lower percentage of cells, 6-21%, showed selectivity based on EPSP size. To study the mechanisms underlying the generation of FM selectivity, we compared FM responses with responses to simple tones in the same cells. We found that if pairs of neurons responded in a similar way to simple tones, they generally also responded in a similar way to FM sweeps. Further evidence that FM selectivity can be generated within the dorsal cortex was obtained by reconstructing FM sweeps from the response to simple tones using three different models. In about half of the direction selective neurons the selectivity was generated by spectrally asymmetric synaptic inhibition. In addition, evidence for direction selectivity based on the timing of excitatory responses was also obtained in some cells. No clear evidence for the local generation of rate selectivity was obtained. We conclude that FM direction selectivity can be generated within the dorsal cortex of the mouse inferior colliculus by multiple mechanisms.

S3 Dorsal Root Ganglion/Nerve Root Stimulation for Refractory Postsurgical Perineal Pain: Technical Aspects of Anchorless Sacral Transforaminal Lead Placement

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X. Zuidema

2016-01-01

Full Text Available Chronic perineal pain limits patients in physical and sexual activities, leading to social and psychological distress. In most cases, this pain develops after surgery in the urogenital area or as a consequence of trauma. Neuromodulation is one of the options in chronic postsurgical perineal pain treatment. We present a case of refractory perineal pain after right sided surgical resection of a Bartholin’s cyst which was treated with third sacral nerve root/dorsal root ganglion stimulation using the transforaminal approach. We describe a new anchorless lead placement technique using a unique curved lead delivery sheath. We postulate that this new posterior foraminal technique of lead placement is simple, safe, and reversible and may lower the occurrence of lead related complications.

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

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Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

2018-01-01

The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

Directory of Open Access Journals (Sweden)

Manojkumar Gunasekaran

2018-04-01

Full Text Available The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR, dorsal root ganglion (DRG sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM into wild-type (WT mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

Lumbar dorsal ramus syndrome.

Science.gov (United States)

Bogduk, N

1980-11-15

Low back pain, referred pain in the lower limbs, and spasm of the back, gluteal, and hamstring muscles are clinical features which can be induced in normal volunteers by stimulating structures which are innervated by the lumbar dorsal rami. Conversely, they can be relieved in certain patients by selective interruption of conduction along dorsal rami. These facts permit the definition of a lumbar dorsal ramus syndrome, which can be distinguished from the intervertebral disc syndrome and other forms of low back pain. The distinguishing feature is that, in lumbar dorsal ramus syndrome, all the clinical features are exclusively mediated by dorsal rami and do not arise from nerve-root compression. The pathophysiology, pathology, and treatment of this syndrome are described. Recognition of this syndrome, and its treatment with relatively minor procedures, can obviate the need for major surgery which might otherwise be undertaken.

A compact dual promoter adeno-associated viral vector for efficient delivery of two genes to dorsal root ganglion neurons

NARCIS (Netherlands)

Fagoe, N D; Eggers, R; Verhaagen, J; Mason, M R J

Adeno-associated viral (AAV) vectors based on serotype 5 are an efficient means to target dorsal root ganglia (DRG) to study gene function in the primary sensory neurons of the peripheral nervous system. In this study, we have developed a compact AAV dual promoter vector composed of the

Antidepressant Imipramine Protects Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Coactivation of TrkA and TrkB.

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Guo, Jianrong; Wang, Huan; Tao, Qiang; Sun, Shiyu; Liu, Li; Zhang, Jianping; Yang, Dawei

2017-11-01

In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)-induced neurotoxicity in mouse dorsal root ganglion (DRG). Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre-treated with Ip, prior to Bv, to examine its effects on protecting Bv-induced DRG apoptosis and neurite degeneration. Ip-induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p-)TrkA/B/C, were examined by qPCR and Western blot. TrkA and TrkB were inhibited by siRNAs to further investigate their functional role in Ip- and Bv-treated DRG. Ip protected Bv-induced apoptosis and neurite loss in DRG. Ip did not alter TrkA/B/C expressions, whereas significantly augmented protein productions of p-TrkA and p-TrkB, but not p-TrkC. SiRNA-mediated TrkA or TrkB downregulation inhibited Trk receptors, and reduced p-TrkA and p-TrkB in DRG. TrkA or TrkB downregulation alone had no effect on Ip-induced protection in Bv-injured DRG. However, co-inhibition of TrkA and TrkB significantly ameliorated the protective effect of Ip on Bv-induced apoptosis and neurite loss in DRG. Imipramine protected bupivacaine-induced neurotoxicity in DRG, likely via the co-activation of TrkA and TrkB signaling pathways. J. Cell. Biochem. 118: 3960-3967, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni

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Partata W.A.

1999-01-01

Full Text Available Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spinal glial and endothelial cells. These findings are discussed in relation to the role of nitric oxide in hyperalgesia and neuronal regeneration or degeneration.

Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni.

Science.gov (United States)

Partata, W A; Krepsky, A M; Marques, M; Achaval, M

1999-04-01

Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spinal glial and endothelial cells. These findings are discussed in relation to the role of nitric oxide in hyperalgesia and neuronal regeneration or degeneration.

Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies.

Science.gov (United States)

Wu, Lisa; Wu, Jun; Chang, Huiyi H; Havton, Leif A

2012-02-01

Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non

EXPRESSION OF CALCIUM-BINDING PROTEINS IN THE NEUROTROPHIN-3-DEPENDENT SUBPOPULATION OF RAT EMBRYONIC DORSAL-ROOT GANGLION-CELLS IN CULTURE

NARCIS (Netherlands)

COPRAY, JCVM; MANTINGHOTTER, IJ; BROUWER, N

1994-01-01

In this study we have examined the calcium-binding protein expression in rat embryonic (E16) dorsal root ganglia (DRG) neurons in vitro in the presence of neurotrophin-3 (NT-3). A comparison was made with the expression of calcium-binding proteins in DRG subpopulations that depended in vitro on

The effects of capsaicin and acidity on currents generated by noxious heat in cultured neonatal rat dorsal root ganglion neurones

Czech Academy of Sciences Publication Activity Database

Vlachová, Viktorie; Lyfenko, Alla; Orkand, R. K.; Vyklický st., Ladislav

2001-01-01

Roč. 533, č. 3 (2001), s. 717-728 ISSN 0022-3751 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : capsaicin * dorsal root ganglion neurones * neonatal rat Subject RIV: FH - Neurology Impact factor: 4.476, year: 2001

Expression of gastrin-releasing peptide by excitatory interneurons in the mouse superficial dorsal horn.

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Gutierrez-Mecinas, Maria; Watanabe, Masahiko; Todd, Andrew J

2014-12-11

Gastrin-releasing peptide (GRP) and its receptor have been shown to play an important role in the sensation of itch. However, although GRP immunoreactivity has been detected in the spinal dorsal horn, there is debate about whether this originates from primary afferents or local excitatory interneurons. We therefore examined the relation of GRP immunoreactivity to that seen with antibodies that label primary afferent or excitatory interneuron terminals. We tested the specificity of the GRP antibody by preincubating with peptides with which it could potentially cross-react. We also examined tissue from a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under control of the GRP promoter. GRP immunoreactivity was seen in both primary afferent and non-primary glutamatergic axon terminals in the superficial dorsal horn. However, immunostaining was blocked by pre-incubation of the antibody with substance P, which is present at high levels in many nociceptive primary afferents. EGFP+ cells in the GRP-EGFP mouse did not express Pax2, and their axons contained the vesicular glutamate transporter 2 (VGLUT2), indicating that they are excitatory interneurons. In most cases, their axons were also GRP-immunoreactive. Multiple-labelling immunocytochemical studies indicated that these cells did not express either of the preprotachykinin peptides, and that they generally lacked protein kinase Cγ, which is expressed by a subset of the excitatory interneurons in this region. These results show that GRP is expressed by a distinct population of excitatory interneurons in laminae I-II that are likely to be involved in the itch pathway. They also suggest that the GRP immunoreactivity seen in primary afferents in previous studies may have resulted from cross-reaction of the GRP antibody with substance P or the closely related peptide neurokinin A.

Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS) Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord Stimulation.

Science.gov (United States)

Goebel, Andreas; Lewis, Sarah; Phillip, Rhodri; Sharma, Manohar

2018-01-01

Limb amputation is sometimes being performed in long-standing complex regional pain syndrome (CRPS), although little evidence is available guiding management decisions, including how CRPS recurrence should be managed. This report details the management of a young soldier with CRPS recurrence 2 years after midtibial amputation for CRPS. Conventional spinal cord stimulation did not achieve paraesthetic coverage, or pain relief in the stump, whereas L4 dorsal root ganglion stimulation achieved both coverage and initially modest pain relief, and over time, substantial pain relief. Current evidence does not support the use of amputation to improve either pain or function in CRPS. Before a decision is made, in exceptional cases, about referral for amputation, dorsal root ganglion stimulation should be considered as a potentially effective treatment, even where conventional spinal cord stimulator treatment has failed to achieve reliable paraesthetic cover. Furthermore, this treatment may provide pain relief in those patients with CRPS recurrence in the stump after amputation. © 2017 World Institute of Pain.

HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection

NARCIS (Netherlands)

Sharthiya, H.; Seng, C.; Kuppevelt, T.H. van; Tiwari, V.; Fornaro, M.

2017-01-01

The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

Science.gov (United States)

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

New Treatments for Spinal Nerve Root Avulsion Injury

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Thomas Carlstedt

2016-08-01

Full Text Available Further progress in the treatment of the longitudinal spinal cord injury has been made. In an inverted translational study, it has been demonstrated that return of sensory function can be achieved by bypassing the avulsed dorsal root ganglion neurons. Dendritic growth from spinal cord sensory neurons could replace dorsal root ganglion axons and re-establish a reflex arch. Another research avenue has led to the development of adjuvant therapy for regeneration following dorsal root to spinal cord implantation in root avulsion injury. A small, lipophilic molecule that can be given orally acts on the retinoic acid receptor system as an agonist. Upregulation of dorsal root ganglion regenerative ability and organization of glia reaction to injury were demonstrated in treated animals. The dual effect of this substance may open new avenues for the treatment of root avulsion and spinal cord injuries.

Assessing the effectiveness of ‘pulse radiofrequency treatment of dorsal root ganglion’ in patients with chronic lumbar radicular pain: study protocol for a randomized control trial

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Shanthanna Harsha

2012-04-01

Full Text Available Abstract Background Chronic lumbar radicular pain can be described as neuropathic pain along the distribution of a particular nerve root. The dorsal root ganglion has been implicated in its pathogenesis by giving rise to abnormal impulse generation as a result of irritation, direct compression and sensitization. Chronic lumbar radicular pain is commonly treated with medications, physiotherapy and epidural steroid injections. Epidural steroid injections are associated with several common and rarer side effects such as spinal cord infarction and death. It is essential and advantageous to look for alternate interventions which could be effective with fewer side effects. Pulse radio frequency is a relatively new technique and is less destructive then conventional radiofrequency. Safety and effectiveness of pulse radio frequency in neuropathic pain has been demonstrated in animal and humans studies. Although its effects on dorsal root ganglion have been studied in animals there is only one randomized control trial in literature demonstrating its effectiveness in cervical radicular pain and none in lumbar radicular pain. Our primary objective is to study the feasibility of a larger trial in terms of recruitment and methodology. Secondary objectives are to compare the treatment effects and side effects. Methods/designs This is a single-center, parallel, placebo-controlled, triple-blinded (patients, care-givers, and outcome assessors, randomized control trial. Participants will have a history of chronic lumbar radicular pain for at least 4 months in duration. Once randomized, all patients will have an intervention involving fluoroscopy guided needle placement to appropriate dorsal root ganglion. After test stimulation in both groups; the study group will have a pulse radio frequency treatment at 42°C for 120 s to the dorsal root ganglion, with the control group having only low intensity test stimulation for the same duration. Primary outcome is to

A Multicenter, Prospective Trial to Assess the Safety and Performance of the Spinal Modulation Dorsal Root Ganglion Neurostimulator System in the Treatment of Chronic Pain

NARCIS (Netherlands)

A.L. Liem (Liong); M. Russo (Marc); F.J.P.M. Huygen (Frank); J.P. Van Buyten (Jean-Pierre); I. Smets (Ilse); P. Verrills (Paul); M. Cousins (Michael); C. Brooker (Charles); R. Levy (Richard); T. Deer (Timothy); J. Kramer (Jeffery)

2013-01-01

textabstractObjectives: This multicenter prospective trial was conducted to evaluate the clinical performance of a new neurostimulation system designed to treat chronic pain through the electrical neuromodulation of the dorsal root ganglia (DRG) neurophysiologically associated with painful regions

In Vitro Analysis of the Role of Schwann Cells on Axonal Degeneration and Regeneration Using Sensory Neurons from Dorsal Root Ganglia.

Science.gov (United States)

López-Leal, Rodrigo; Diaz, Paula; Court, Felipe A

2018-01-01

Sensory neurons from dorsal root ganglion efficiently regenerate after peripheral nerve injuries. These neurons are widely used as a model system to study degenerative mechanisms of the soma and axons, as well as regenerative axonal growth in the peripheral nervous system. This chapter describes techniques associated to the study of axonal degeneration and regeneration using explant cultures of dorsal root ganglion sensory neurons in vitro in the presence or absence of Schwann cells. Schwann cells are extremely important due to their involvement in tissue clearance during axonal degeneration as well as their known pro-regenerative effect during regeneration in the peripheral nervous system. We describe methods to induce and study axonal degeneration triggered by axotomy (mechanical separation of the axon from its soma) and treatment with vinblastine (which blocks axonal transport), which constitute clinically relevant mechanical and toxic models of axonal degeneration. In addition, we describe three different methods to evaluate axonal regeneration using quantitative methods. These protocols constitute a valuable tool to analyze in vitro mechanisms associated to axonal degeneration and regeneration of sensory neurons and the role of Schwann cells in these processes.

Postoperative visual loss following dorsal root entry zone rhizotomy: A dreaded complication after a benign procedure

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R K Mishra

2016-01-01

Full Text Available Postoperative visual loss (POVL is a rare but grave postoperative complication. It has been mainly reported in patients undergoing cardiac and spinal surgeries. Dorsal root entry zone (DREZ is pain relieving procedure performed in patients with refractory neuropathic pain with minimal complication rate. We present a case of unilateral POVL following DREZ rhizotomy in prone position in a patient having brachial plexus neuropathy. Exact etiology of vision loss was though not clear; hypotension, use of vasopressors and hemodilution may have led to vision loss in this patient. This case report highlights the associated risk factors for development of this hazardous complication.

Uso terapêutico da radiofrequência pulsátil no gânglio dorsal da raiz de L2 na lombalgia discogênica Uso terapéutico de la radiofrecuencia pulsátil en el ganglio dorsal de la raíz de L2 en la lumbalgia discogénica Pulsed radiofrequency on L2 dorsal root ganglion as a therapeutic method for lumbar discogenic pain

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Fabrício Dias Assis

2009-06-01

Full Text Available OBJETIVO: Avaliar a eficácia da radiofrequência pulsátil sobre o gânglio da raiz dorsal de L2 no tratamento dos pacientes com lombalgia discogênica. MÉTODOS: Realizou-se análise retrospectiva de 50 pacientes portadores de lombalgia crônica discogênica atendidos no período de janeiro de 2004 a julho de 2007. O processo diagnóstico foi constituído por exame físico, ressonância magnética e bloqueio diagnóstico do gânglio da raiz dorsal de L2. Todos os pacientes foram submetidos à radiofrequência pulsátil no gânglio da raiz dorsal de L2 e acompanhados por, no mínimo, 12 meses. A intensidade de dor foi medida pela escala visual analógica (EVA de dor. RESULTADOS: A análise estatística mostrou melhora significativa da intensidade de dor (pOBJETIVO: evaluar la eficacia de la radiofrecuencia pulsátil sobre el ganglio de la raíz dorsal de L2 en el tratamiento de los pacientes con lumbalgia discogénica. MÉTODOS: fue realizado un análisis retrospectivo de 50 pacientes portadores de lumbalgia crónica discogénica, atendidos en el periodo de Enero de 2004 a Julio de 2007. El proceso diagnóstico constó de un examen físico, resonancia magnética y bloqueo diagnóstico del ganglio de la raíz dorsal de L2. Todos los pacientes fueron sometidos a la radiofrecuencia pulsátil en el ganglio de la raíz dorsal de L2 y seguidos por 12 meses, como mínimo. La intensidad del dolor fue medida por la escala visual analógica del dolor. RESULTADOS: el análisis estadístico mostró mejoría significativa de la intensidad del dolor (pOBJECTIVE: to evaluate the effectiveness of pulsate radio-frequency on L2 dorsal root ganglion for chronic discogenic low back pain. Of L2 in the treatment of the patient with discogenic low back pain. METHODS: Between January 2004 and July 2007, 50 patients with diagnosis of low back discogenic pain were retrospectively assessed based on physical examination, magnetic resonance imaging findings and selective L

Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

DEFF Research Database (Denmark)

Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

2001-01-01

neurogenesis seemed initially normal. A degeneration of motoneurons and sensory neurons occurred later in development. The mechanism that leads to the dramatic effects on the neural crest derived cell lineages in the dorsal root ganglia (DRG), however, has not been examined up to now. Here, we provide...... a detailed analysis of proliferation and apoptosis in the DRG during the time of their generation and lineage segregation (between E 9.5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism....

[Effect of bee venom injection on TrkA and TRPV1 expression in the dorsal root ganglion of rats with collagen-induced arthritis].

Science.gov (United States)

Xian, Pei-Feng; Chen, Ying; Yang, Lu; Liu, Guo-Tao; Peng, Peng; Wang, Sheng-Xu

2016-06-01

To investigate the therapeutic effect of acupoint injection of bee venom on collagen-induced arthritis (CIA) in rats and explore the mechanism of bee venom therapy in the treatment of rheumatoid arthritis. Fifteen male Wistar rats were randomly divided into bee venom treatment group (BV group), CIA model group, and control group. In the former two groups, CIA was induced by injections of collagen II+IFA (0.2 mL) via the tail vein, and in the control group, normal saline was injected instead. The rats in BV group received daily injection of 0.1 mL (3 mg/mL) bee venom for 7 consecutive days. All the rats were assessed for paw thickness and arthritis index from days 14 to 21, and the pain threshold was determined on day 21. The expressions of TRPV1 and TrkA in the dorsal root ganglion at the level of L4-6 were detected using immunohistochemistry and Western blotting, respectively. The rats in CIA model group started to show paw swelling on day 10, and by day 14, all the rats in this group showed typical signs of CIA. In BV group, the rats receiving been venom therapy for 7 days showed a significantly smaller paw thickness and a low arthritis index than those in the model group. The pain threshold was the highest in the control group and the lowest in the model group. TRPV1-positive cells and TrkA expression in the dorsal root ganglion was significantly reduced in BV group as compared with that in the model group. s Injection of bee venom can decrease expression of TRPV1 and TrkA in the dorsal root ganglion to produce anti-inflammatory and analgesic effects, suggesting the potential value of bee venom in the treatment of rheumatoid arthritis.

Neuroimmune and Neuropathic Responses of Spinal Cord and Dorsal Root Ganglia in Middle Age

Science.gov (United States)

Galbavy, William; Kaczocha, Martin; Puopolo, Michelino; Liu, Lixin; Rebecchi, Mario J.

2015-01-01

Prior studies of aging and neuropathic injury have focused on senescent animals compared to young adults, while changes in middle age, particularly in the dorsal root ganglia (DRG), have remained largely unexplored. 14 neuroimmune mRNA markers, previously associated with peripheral nerve injury, were measured in multiplex assays of lumbar spinal cord (LSC), and DRG from young and middle-aged (3, 17 month) naïve rats, or from rats subjected to chronic constriction injury (CCI) of the sciatic nerve (after 7 days), or from aged-matched sham controls. Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults. Similarly, LSC samples from older sham animals showed increased levels of T-cell and microglial/macrophage markers. CCI induced further increases in CCL2, and IL6, and elevated ATF3 mRNA levels in LSC of young and middle-aged adults. Immunofluorescence images of dorsal horn microglia from middle-aged naïve or sham rats were typically hypertrophic with mostly thickened, de-ramified processes, similar to microglia following CCI. Unlike the spinal cord, marker expression profiles in naïve DRG were unchanged across age (except increased ATF3); whereas, levels of GFAP protein, localized to satellite glia, were highly elevated in middle age, but independent of nerve injury. Most neuroimmune markers were elevated in DRG following CCI in young adults, yet middle-aged animals showed little response to injury. No age-related changes in nociception (heat, cold, mechanical) were observed in naïve adults, or at days 3 or 7 post-CCI. The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG. These changes, however, did not

PKA-induced internalization of slack KNa channels produces dorsal root ganglion neuron hyperexcitability.

Science.gov (United States)

Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

2010-10-20

Inflammatory mediators through the activation of the protein kinase A (PKA) pathway sensitize primary afferent nociceptors to mechanical, thermal, and osmotic stimuli. However, it is unclear which ion conductances are responsible for PKA-induced nociceptor hyperexcitability. We have previously shown the abundant expression of Slack sodium-activated potassium (K(Na)) channels in nociceptive dorsal root ganglion (DRG) neurons. Here we show using cultured DRG neurons, that of the total potassium current, I(K), the K(Na) current is predominantly inhibited by PKA. We demonstrate that PKA modulation of K(Na) channels does not happen at the level of channel gating but arises from the internal trafficking of Slack channels from DRG membranes. Furthermore, we found that knocking down the Slack subunit by RNA interference causes a loss of firing accommodation analogous to that observed during PKA activation. Our data suggest that the change in nociceptive firing occurring during inflammation is the result of PKA-induced Slack channel trafficking.

The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons

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Douglas M. Lopes

2017-09-01

Full Text Available The dorsal root ganglia (DRG and trigeminal ganglia (TG are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.

Clinical significance of the position of dorsal root ganglia in degenerative lumbar diseases. Correlation between anatomic study and imaging study with MRI

Energy Technology Data Exchange (ETDEWEB)

Seki, Masahiro; Kikuchi, Tomiichi [Fukushima Medical Coll., Matsuoka (Japan)

1995-06-01

In order to estimate the ralationship between the position of dorsal root ganglia (DRG) and radicular symptoms, anatomical study was done on 81 cadavers, and a clinical study with MRI was done on 20 cases of lumbar disc herniation and 20 of lumbar spondylosis with L{sub 5} radiculopathy. The position of DRG is not related to the occurrence of radicular symptoms in disc herniation, while in lumbar spondylosis proximally placed DRG are related to both of unilateral and bilateral occurrence of redicular symptoms. Unilateral occurrence of radicular symptoms is influenced by surrounding tissues of the nerve root, rather than the position of DRG. (author).

Clinical significance of the position of dorsal root ganglia in degenerative lumbar diseases. Correlation between anatomic study and imaging study with MRI

International Nuclear Information System (INIS)

Seki, Masahiro; Kikuchi, Tomiichi

1995-01-01

In order to estimate the ralationship between the position of dorsal root ganglia (DRG) and radicular symptoms, anatomical study was done on 81 cadavers, and a clinical study with MRI was done on 20 cases of lumbar disc herniation and 20 of lumbar spondylosis with L 5 radiculopathy. The position of DRG is not related to the occurrence of radicular symptoms in disc herniation, while in lumbar spondylosis proximally placed DRG are related to both of unilateral and bilateral occurrence of redicular symptoms. Unilateral occurrence of radicular symptoms is influenced by surrounding tissues of the nerve root, rather than the position of DRG. (author)

Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

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Takayoshi eMasuoka

2016-03-01

Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

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Coutinho-Budd, Jaeda C; Snider, Samuel B; Fitzpatrick, Brendan J; Rittiner, Joseph E; Zylka, Mark J

2013-09-08

Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons. We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12. Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.

Whole transcriptome expression of trigeminal ganglia compared to dorsal root ganglia in Rattus Norvegicus

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Kogelman, Lisette Johanna Antonia; Christensen, Rikke Elgaard; Pedersen, Sara Hougaard

2017-01-01

The trigeminal ganglia (TG) subserving the head and the dorsal root ganglia (DRG) subserving the rest of the body are homologous handling sensory neurons. Differences exist, as a number of signaling substances cause headache but no pain in the rest of the body. To date, very few genes involved...... in this difference have been identified. We aim to reveal basal gene expression levels in TG and DRG and detect genes that are differentially expressed (DE) between TG and DRG. RNA-Sequencing from six naïve rats describes the whole transcriptome expression profiles of TG and DRG. Differential expression analysis...... was followed by pathway analysis to identify DE processes between TG and DRG. In total, 64 genes had higher and 55 genes had lower expressed levels in TG than DRG. Higher expressed genes, including S1pr5 and Gjc2, have been related to phospholipase activity. The lower expressed genes, including several Hox...

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

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Vargas-Alarcon Gilberto

2012-02-01

Full Text Available Abstract Background A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM; and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7 act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ. Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036 mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88 than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002 and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001. Conclusion In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that

Multimodality pH imaging in a mouse dorsal skin fold window chamber model

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Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

2013-03-01

Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

Changes in galanin immunoreactivity in rat lumbosacral spinal cord and dorsal root ganglia after spinal cord injury.

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Zvarova, K; Murray, E; Vizzard, M A

2004-08-02

Alterations in the expression of the neuropeptide galanin were examined in micturition reflex pathways 6 weeks after complete spinal cord transection (T8). In control animals, galanin expression was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the superficial dorsal horn; (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1); and (4) the lateral collateral pathway in lumbosacral spinal segments. Densitometry analysis demonstrated significant increases (P < or = 0.001) in galanin immunoreactivity (IR) in these regions of the S1 spinal cord after spinal cord injury (SCI). Changes in galanin-IR were not observed at the L4-L6 segments except for an increase in galanin-IR in the dorsal commissure in the L4 segment. In contrast, decreases in galanin-IR were observed in the L1 segment. The number of galanin-IR cells increased (P < or = 0.001) in the L1 and S1 dorsal root ganglia (DRG) after SCI. In all DRG examined (L1, L2, L6, and S1), the percentage of bladder afferent cells expressing galanin-IR significantly increased (4-19-fold) after chronic SCI. In contrast, galanin expression in nerve fibers in the urinary bladder detrusor and urothelium was decreased or eliminated after SCI. Expression of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was altered in the spinal cord after SCI. A significant increase in BDNF expression was present in spinal cord segments after SCI. In contrast, NGF expression was only increased in the spinal segments adjacent and rostral to the transection site (T7-T8), whereas spinal segments (T13-L1; L6-S1), distal to the transection site exhibited decreased NGF expression. Changes in galanin expression in micturition pathways after SCI may be mediated by changing neurotrophic factor expression, particularly BDNF. These changes may contribute to

Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

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Fernández, A; Radmilovich, M; Russo, R E

1996-01-01

This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have...

Oxaliplatin-Induced Peripheral Neuropathy via TRPA1 Stimulation in Mice Dorsal Root Ganglion Is Correlated with Aluminum Accumulation.

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Jin-Hee Park

Full Text Available Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy, or as abnormal sensory or motor function (chronic neuropathy. In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest, we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl3∙6H2O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice.

The inhibiting effects of Urtica dioica root extracts on experimentally induced prostatic hyperplasia in the mouse.

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Lichius, J J; Muth, C

1997-08-01

Extracts of stinging nettle roots (Urtica dioica L. Urticaceae) are used in the treatment of benign prostatic hyperplasia (BPH). We established a BPH-model by directly implanting an urogenital sinus (UGS) into the ventral prostate gland of an adult mouse. Five differently prepared stinging nettle root extracts were tested in this model. The 20% methanolic extract was the most effective with a 51.4% inhibition of induced growth.

[Effects of small needle knife on the substance P in the dorsal root ganglion and spinal cord of rats].

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Wang, Jin-Rong; Wang, Yong-Zhi; Dong, Fu-Hui; Zhong, Hong-Gang; Wang, De-Long; Wang, Xuan

2010-09-01

To study the mechanism of synthesis of substance P (SP) in the dorsal root ganglion (DRG) and the release of it in the dorsal horn of the spinal cord of rats after compression of skeletal muscle, and to observe the influence of small needle knife. Sustained pressure of 70 kPa was applied to rats, muscular tissues for 2 hours. The rats were divided into three groups: normal, control and experiment group respectively. In all rats except the six normal ones, the lower legs were compressed once one day. The left leg was considered as the control group, the right left was experiment group, which were divided into the 1st day, the 2nd day and the 3rd day within the two groups. Experiment group was treated with small needle knife after the muscular tissue was compressed. After completing the stimulation, the DRG related to the muscle and part of spinal cord were removed for the qualification of SP-like immunoreactivity using immunohistochemistry. The dark brown stains on the DRG and on the REXed laminae I and II in the dorsal horn of the spinal cord were counted by Image-Pro Plus software. SP-like immunoreactivity in the side treated by the small needle knife was enhanced comparing with the counterpart in DRG in normal group (P DRG in the experiment group were significantly reduced compared with the control group (P DRG, and shows no effects on the release of SP from the spinal cord in short-term (3 days).

Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain.

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Levine, Adrian B; Parrent, Andrew G; MacDougall, Keith W

2017-01-01

Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of ≥50% during trial stimulation. Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained ≥50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs.

Identification of dorsal root synaptic terminals on monkey ventral horn cells by electron microscopic autoradiography

International Nuclear Information System (INIS)

Ralston, H.J.; Ralston, D.D.

1979-01-01

The projection of dorsal root fibres to the motor nucleus of the macaque monkey spinal cord has been examined utilizing light and electron microscopic autoradiography. Light microscopy demonstrates a very sparse labelling of primary afferent fibres in the ventral horn. Silver grains overlying radioactive sources are frequently clustered into small groups, often adjacent to dendritic profiles. Under the electron microscope, myelinated axons and a few large synaptic profiles containing rounded synaptic vesicles were overlain by numerous silver grains. These labelled profiles made synaptic contact with dendrites 1 - 3 micrometers in diameter. The labelled profiles did not contact cell bodies or large proximal dendrites of ventral horn neutrons. Frequently, small synaptic profiles containing flattened vesicles were presynaptic to the large labelled terminals and it is suggested that these axoaxonal synapses may mediate presynaptic inhibition of the primary afferent fibres. The relationship of the present findings to previously published physiological and anatomical studies is discussed. (author)

The effects of anticonvulsants on 4-aminopyridine-induced bursting: in vitro studies on rat peripheral nerve and dorsal roots.

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Lees, G.

1996-01-01

1. Aminopyridines have been used as beneficial symptomatic treatments in a variety of neurological conditions including multiple sclerosis but have been associated with considerable toxicity in the form of abdominal pain, paraesthesias and (rarely) convulsions. 2. Extracellular and intracellular recording was used to characterize action potentials in rat sciatic nerves and dorsal roots and the effects of 4-aminopyridine (4-AP). 3. In sciatic nerve trunks, 1 mM 4-AP produced pronounced after potentials at room temperature secondary to regenerative firing in affected axons (5-10 spikes per stimulus). At physiological temperatures, after potentials (2-3 spikes) were greatly attenuated in peripheral axons. 4. 4-AP evoked more pronounced and prolonged after discharges in isolated dorsal roots at 37 degrees C (3-5.5 mV and 80-100 ms succeeded by a smaller inhibitory/depolarizing voltage shift) which were used to assess the effects of anticonvulsants. 5. Phenytoin, carbamazepine and lamotrigine dose-dependently reduced the area of 4-AP-induced after potentials at 100 and 320 microM but the amplitude of compound action potentials (evoked at 0.5 Hz) was depressed in parallel. 6. The tonic block of sensory action potentials by all three drugs (at 320 microM) was enhanced by high frequency stimulation (5-500 Hz). 7. The lack of selectivity of these frequency-dependent Na+ channel blockers for burst firing compared to low-frequency spikes, is discussed in contrast to their effects on 4-AP-induced seizures and paroxysmal activity in CNS tissue (which is associated with large and sustained depolarizing plateau potentials). 8. In conclusion, these in vitro results confirm the marked sensitivity of sensory axons to 4-AP (the presumptive basis for paraesthesias). Burst firing was not preferentially impaired at relatively high concentrations suggesting that anticonvulsants will not overcome the toxic peripheral actions of 4-AP in neurological patients. PMID:8821551

Growth of rat dorsal root ganglion neurons on a novel self-assembling scaffold containing IKVAV sequence

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Zou Zhenwei; Zheng Qixin [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China); Wu Yongchao, E-mail: wuyongchao@hotmail.com [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China); Song Yulin; Wu Bin [Department of Orthopaedics, Union Hospital, Tongji Medical college of Huazhong University of science and technology, Wuhan, 430022 (China)

2009-08-31

The potential benefits of self-assembly in synthesizing materials for the treatment of both peripheral and central nervous system disorders are tremendous. In this study, we synthesized peptide-amphiphile (PA) molecules containing IKVAV sequence and induced self-assembly of the PA solutions in vitro to form nanofiber gels. Then, we tested the characterization of gels by transmission electron microscopy and demonstrated the biocompatibility of this gel towards rat dorsal root ganglion neurons. The nanofiber gel was formed by self-assembly of IKVAV PA molecules, which was triggered by metal ions. The fibers were 7-8 nm in diameter and with lengths of hundreds of nanometers. Gels were shown to be non-toxic to neurons and able to promote neurons adhesion and neurite sprouting. The results indicated that the self-assembling scaffold containing IKVAV sequence had excellent biocompatibility with adult sensory neurons and could be useful in nerve tissue engineering.

Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

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Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

2017-01-01

The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey.

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Darian-Smith, Corinna

2004-03-01

We examined the role of primary afferent neurons in the somatosensory cortical "reactivation" that occurs after a localized cervical dorsal root lesion (Darian-Smith and Brown [2000] Nat. Neurosci. 3:476-481). After section of the dorsal rootlets that enervate the macaque's thumb and index finger (segments C6-C8), the cortical representation of these digits was initially silenced but then re-emerged for these same digits over 2-4 postlesion months. Cortical reactivation was accompanied by the emergence of physiologically detectable input from these same digits within dorsal rootlets bordering the lesion site. We investigated whether central axonal sprouting of primary afferents spared by the rhizotomy could mediate this cortical reactivation. The cortical representation of the hand was mapped electrophysiologically 15-25 weeks after the dorsal rootlet section to define this reactivation. Cholera toxin subunit B conjugated to horseradish peroxidase was then injected into the thumb and index finger pads bilaterally to label the central terminals of any neurons that innervated these digits. Primary afferent terminal proliferation was assessed in the spinal dorsal horn and cuneate nucleus at 7 days and 15-25 postlesion weeks. Labeled terminal bouton distributions were reconstructed and the "lesion" and control sides compared within each monkey. Distributions were significantly larger on the side of the lesion in the dorsal horn and cuneate nucleus at 15-25 weeks after the dorsal rootlet section, than those mapped only 7 days postlesion. Our results provide direct evidence for localized sprouting of spared (uninjured) primary afferent terminals in the dorsal horn and cuneate nucleus after a restricted dorsal root injury. Copyright 2004 Wiley-Liss, Inc.

Effect of low level laser therapy on chronic compression of the dorsal root ganglion.

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Yi-Jen Chen

Full Text Available Dorsal root ganglia (DRG are vulnerable to physical injury of the intervertebral foramen, and chronic compression of the DRG (CCD an result in nerve root damage with persistent morbidity. The purpose of this study was to evaluate the effects of low level laser therapy (LLLT on the DRG in a CCD model and to determine the mechanisms underlying these effects. CCD rats had L-shaped stainless-steel rods inserted into the fourth and fifth lumbar intervertebral foramen, and the rats were then subjected to 0 or 8 J/cm2 LLLT for 8 consecutive days following CCD surgery. Pain and heat stimuli were applied to test for hyperalgesia following CCD. The levels of TNF-α, IL-1β and growth-associated protein-43 (GAP-43 messenger RNA (mRNA expression were measured via real-time PCR, and protein expression levels were analyzed through immunohistochemical analyses. Our data indicate that LLLT significantly decreased the tolerable sensitivity to pain and heat stimuli in the CCD groups. The expression levels of the pro-inflammatory cytokines TNF-α and IL-1β were increased following CCD, and we found that these increases could be reduced by the application of LLLT. Furthermore, the expression of GAP-43 was enhanced by LLLT. In conclusion, LLLT was able to enhance neural regeneration in rats following CCD and improve rat ambulatory behavior. The therapeutic effects of LLLT on the DRG during CCD may be exerted through suppression of the inflammatory response and induction of neuronal repair genes. These results suggest potential clinical applications for LLLT in the treatment of compression-induced neuronal disorders.

[Selective cervical dorsal root cutting off part of the vertebral lateral mass fixation combined with exercise therapy for treating spastic cerebral paralysis of the upper limbs caused by cerebral palsy].

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Zhang, Peng; Hu, Wei; Cao, Xu; Xu, Shi-gang; Li, De-kui; Xu, Lin

2009-10-01

To explore the feasibility and the result for the surgical treatment of spastic cerebral paralysis of the upper limbs in patients who underwent the selective cervical dorsal root cutting off part of the vertebral lateral mass fixation combined with exercise therapy. From March 2004 to April 2008, 27 patients included 19 boys and 8 girls, aging 13-21 years with an average of 15 years underwent selective cervical dorsal root cutting off part of the vertebral lateral mass fixation with exercise therapy. The AXIS 8 holes titanium plate was inserted into the lateral mass of spinous process through guidance of the nerve stimulator, choosed fasciculus of low-threshold nerve dorsal root and cut off its 1.5 cm. After two weeks, training exercise therapy was done in patients. Training will include lying position, turning body, sitting position, crawling, kneeling and standing position, walking and so on. Spastic Bobath inhibiting abnormal pattern was done in the whole process of training. The muscular tension, motor function (GMFM), functional independence (WeeFIM) were observed after treatment. All patients were followed up from 4 to 16 months with an average of 6 months. Muscular tension score were respectively 3.30 +/- 0.47 and 1.25 +/- 0.44 before and after treatment;GMFM score were respectively 107.82 +/- 55.17 and 131.28 +/- 46.45; WeeFIM score were respectively 57.61 +/- 25.51 and 87.91 +/- 22.39. There was significant improvement before and after treatment (P cerebral paralysis of the upper limbs is safe and effective method, which can decrease muscular tension and improve motor function, which deserves more wide use.

Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain.

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Pan, Weixing X; Mao, Tianyi; Dudman, Joshua T

2010-01-01

The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

Gastroprotective effect of Desmodium gangeticum roots on gastric ulcer mouse models

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Ayyavu Mahesh

2012-06-01

Full Text Available In the present study, the ethanolic root extract of Desmodium gangeticum (L. DC., Fabaceae, (EDG, have been studied in various acute and chronic ulcer mouse models. Oral administration of root extract, significantly decrease the ulcer index and lesion number in a dose dependent manner against ethanol induced acute gastric ulcer in mice. In gastric ulcerated animal that received high dose of 150 mg/kg EDG, the mucosa showed no ulceration with slight focal congestion and the glands appeared normal. Pylorus ligated mice, pretreated with EDG showed significant decrease in ulcerous activity under chronic condition. The highest dose (150 mg/kg of the extract provoked a marked increase in protein and glutathione levels, when compare to control. Furthermore, gastric juice, free acidity and total acid output were inhibited in a dose-dependent manner at p<0.05 level. Our results indicate that the EDG possess gastroprotective activity and increasing regeneration of damaged gastric mucosa and thus safe for human use.

Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

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Chiaki Murayama

2015-08-01

Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

Intrathecal ligaments and nerve root tension: possible sources of lumbar pain during spaceflight.

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Kershner, David; Binhammer, Robert

2004-04-01

Lumbar intrathecal ligaments have recently been demonstrated to randomly bind dorsal nerve roots to the dura within the lumbar vertebral column. Lengthening of the vertebral column and associated lumbar back pain experienced by astronauts is common in microgravity. This study was designed to investigate the relationship of lumbar intrathecal ligaments in spinal lengthening as a possible mechanism for back pain. A two-part study was designed using 36 vertebral columns from embalmed cadavers. There were 12 vertebral columns studied in mid-sagittal section to demonstrate the possible movement of the spinal cord during lengthening of the vertebral column. The remainder were assessed for the amount of tension placed on a dorsal nerve root by the lumbar intrathecal ligament during lengthening of the vertebral column. The spinal cord moves in a cephalic direction approximately 2.8 mm with 4 cm lengthening of the vertebral column. During lengthening, a loss of thoracic and lordotic curvature was noted with an increase in disk height. Tension was significantly increased on the dorsal nerve roots being tethered by the lumbar intrathecal ligaments in comparison to non-tethered nerve roots during lengthening of the vertebral column. A significant amount of tension is placed on dorsal nerve roots tethered by intrathecal ligaments within the lumbar spine during spinal lengthening. These ligaments randomly bind dorsal nerve roots in the lumbar spine and may be involved in the back pain experienced by astronauts in microgravity.

Lentiviral gene transfer into the dorsal root ganglion of adult rats

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Park Frank

2011-08-01

Full Text Available Abstract Background Lentivector-mediated gene delivery into the dorsal root ganglion (DRG is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells in vitro and adult rat DRG in vivo. Results In vitro, lentivectors expressing enhanced green fluorescent protein (EGFP under control of the human elongation factor 1α (EF1α promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs, and into primary cultured DRG neurons at higher MOIs. In vivo, injection of either first or second-generation EF1α-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 ± 9% and 20 ± 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons. Conclusion VSV-G pseudotyped lentivectors containing the human elongation factor 1α (EF1α-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain.

Inputs to the dorsal striatum of the mouse conserve the parallel circuit architecture of the forebrain

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Weixing X Pan

2010-12-01

Full Text Available The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and, manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

The effects of canine bone marrow stromal cells on neuritogenesis from dorsal root ganglion neurons in vitro.

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Kamishina, Hiroaki; Cheeseman, Jennifer A; Clemmons, Roger M

2009-10-01

The present in vitro study was designed to evaluate whether canine bone marrow stromal cells (BMSCs) promote neurite outgrowth from dorsal root ganglion (DRG) neurons. Bone marrow aspirates were collected from iliac crests of three young adult dogs. DRG neurons were cultured on BMSCs, fibroblasts, or laminin substrates. DRG neurons were also cultured in BMSC- or fibroblast-conditioned media. DRG neurons grown on BMSCs extended longer neurites and developed a much more elaborate conformation of branching neurites compared to those on fibroblasts or laminin. Quantitative analysis revealed that these effects were associated with the emergence of increased numbers of primary and branching neurites. The effect appears to be dependent upon cell-cell interactions rather than by elaboration of diffusible molecules. With more extensive investigations into the basic biology of canine BMSCs, their ability for promoting neurite outgrowth may be translated into a novel therapeutic strategy for dogs with a variety of neurological disorders.

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

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Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Comprehensive Method for Culturing Embryonic Dorsal Root Ganglion Neurons for Seahorse Extracellular Flux XF24 Analysis.

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Lange, Miranda; Zeng, Yan; Knight, Andrew; Windebank, Anthony; Trushina, Eugenia

2012-01-01

Changes in mitochondrial dynamics and function contribute to progression of multiple neurodegenerative diseases including peripheral neuropathies. The Seahorse Extracellular Flux XF24 analyzer provides a comprehensive assessment of the relative state of glycolytic and aerobic metabolism in live cells making this method instrumental in assessing mitochondrial function. One of the most important steps in the analysis of mitochondrial respiration using the Seahorse XF24 analyzer is plating a uniform monolayer of firmly attached cells. However, culturing of primary dorsal root ganglion (DRG) neurons is associated with multiple challenges, including their propensity to form clumps and detach from the culture plate. This could significantly interfere with proper analysis and interpretation of data. We have tested multiple cell culture parameters including coating substrates, culture medium, XF24 microplate plastics, and plating techniques in order to optimize plating conditions. Here we describe a highly reproducible method to obtain neuron-enriched monolayers of securely attached dissociated primary embryonic (E15) rat DRG neurons suitable for analysis with the Seahorse XF24 platform.

Comprehensive method for culturing embryonic dorsal root ganglion neurons for Seahorse Extracellular Flux XF24 Analysis

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Miranda L. Lange

2012-12-01

Full Text Available Changes in mitochondrial dynamics and function contribute to progression of multiple neurodegenerative diseases including peripheral neuropathies. The Seahorse Extracellular Flux XF24 analyzer provides a comprehensive assessment of the relative state of glycolytic and aerobic metabolism in live cells making this method instrumental in assessing mitochondrial function. One of the most important steps in the analysis of mitochondrial respiration using the Seahorse XF24 analyzer is plating a uniform monolayer of firmly attached cells. However, culturing of primary dorsal root ganglion (DRG neurons is associated with multiple challenges, including their propensity to form clumps and detach from the culture plate. This could significantly interfere with proper analysis and interpretation of data. We have tested multiple cell culture parameters including coating substrates, culture medium, XF24 microplate plastics, and plating techniques in order to optimize plating conditions. Here we describe a highly reproducible method to obtain neuron-enriched monolayers of securely attached dissociated primary embryonic (E15 rat DRG neurons suitable for analysis with the Seahorse XF24 platform.

Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations

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Chengcheng Huang

2017-06-01

Full Text Available Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG. As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD. The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.

Enrichment and proteomic analysis of plasma membrane from rat dorsal root ganglions

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Lin Yong

2009-11-01

Full Text Available Abstract Background Dorsal root ganglion (DRG neurons are primary sensory neurons that conduct neuronal impulses related to pain, touch and temperature senses. Plasma membrane (PM of DRG cells plays important roles in their functions. PM proteins are main performers of the functions. However, mainly due to the very low amount of DRG that leads to the difficulties in PM sample collection, few proteomic analyses on the PM have been reported and it is a subject that demands further investigation. Results By using aqueous polymer two-phase partition in combination with high salt and high pH washing, PMs were efficiently enriched, demonstrated by western blot analysis. A total of 954 non-redundant proteins were identified from the plasma membrane-enriched preparation with CapLC-MS/MS analysis subsequent to protein separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE or shotgun digestion. 205 (21.5% of the identified proteins were unambiguously assigned as PM proteins, including a large number of signal proteins, receptors, ion channel and transporters. Conclusion The aqueous polymer two-phase partition is a simple, rapid and relatively inexpensive method. It is well suitable for the purification of PMs from small amount of tissues. Therefore, it is reasonable for the DRG PM to be enriched by using aqueous two-phase partition as a preferred method. Proteomic analysis showed that DRG PM was rich in proteins involved in the fundamental biological processes including material exchange, energy transformation and information transmission, etc. These data would help to our further understanding of the fundamental DRG functions.

Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.

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Light, Alan R; Hughen, Ronald W; Zhang, Jie; Rainier, Jon; Liu, Zhuqing; Lee, Jeewoo

2008-09-01

The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

Ultrastructural comparison of single dose hydroxyurea and ionizing radiation on mouse hair roots

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Pearson, R.W.; Malkinson, F.D.

1986-01-01

Growing mouse vibrissae were investigated by light and electron microscopy to compare the effects of hydroxyurea (1500 mgkg/sup -1/ intraperitoneally) and gamma radiation (10 Gy). In the case of the drug, specimens were obtained from 30 min to 9 days post-treatment. Irradiated specimens were taken at intervals up to 1.5 years post-irradiation. The morphological alterations were similar for both types of insult, but the time sequences of events were quite different. The post-irradiation recovery period was vastly extended compared with that of the hydroxyurea treated hair roots.

Ultrastructural comparison of single dose hydroxyurea and ionizing radiation on mouse hair roots

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Pearson, R.W.; Malkinson, F.D.

1986-01-01

Growing mouse vibrissae were investigated by light and electron microscopy to compare the effects of hydroxyurea (1500 mgkg -1 intraperitoneally) and gamma radiation (10 Gy). In the case of the drug, specimens were obtained from 30 min to 9 days post-treatment. Irradiated specimens were taken at intervals up to 1.5 years post-irradiation. The morphological alterations were similar for both types of insult, but the time sequences of events were quite different. The post-irradiation recovery period was vastly extended compared with that of the hydroxyurea treated hair roots. (UK)

Neuronal and glial expression of inward rectifier potassium channel subunits Kir2.x in rat dorsal root ganglion and spinal cord.

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Murata, Yuzo; Yasaka, Toshiharu; Takano, Makoto; Ishihara, Keiko

2016-03-23

Inward rectifier K(+) channels of the Kir2.x subfamily play important roles in controlling the neuronal excitability. Although their cellular localization in the brain has been extensively studied, only a few studies have examined their expression in the spinal cord and peripheral nervous system. In this study, immunohistochemical analyses of Kir2.1, Kir2.2, and Kir2.3 expression were performed in rat dorsal root ganglion (DRG) and spinal cord using bright-field and confocal microscopy. In DRG, most ganglionic neurons expressed Kir2.1, Kir2.2 and Kir2.3, whereas satellite glial cells chiefly expressed Kir2.3. In the spinal cord, Kir2.1, Kir2.2 and Kir2.3 were all expressed highly in the gray matter of dorsal and ventral horns and moderately in the white matter also. Within the gray matter, the expression was especially high in the substantia gelatinosa (lamina II). Confocal images obtained using markers for neuronal cells, NeuN, and astrocytes, Sox9, showed expression of all three Kir2 subunits in both neuronal somata and astrocytes in lamina I-III of the dorsal horn and the lateral spinal nucleus of the dorsolateral funiculus. Immunoreactive signals other than those in neuronal and glial somata were abundant in lamina I and II, which probably located mainly in nerve fibers or nerve terminals. Colocalization of Kir2.1 and 2.3 and that of Kir2.2 and 2.3 were present in neuronal and glial somata. In the ventral horn, motor neurons and interneurons were also immunoreactive with the three Kir2 subunits. Our study suggests that Kir2 channels composed of Kir2.1-2.3 subunits are expressed in neuronal and glial cells in the DRG and spinal cord, contributing to sensory transduction and motor control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Conjoined lumbosacral nerve roots

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Kyoshima, Kazumitsu; Nishiura, Iwao; Koyama, Tsunemaro

1986-01-01

Several kinds of the lumbosacral nerve root anomalies have already been recognized, and the conjoined nerve roots is the most common among them. It does not make symptoms by itself, but if there is a causation of neural entrapment, for example, disc herniation, lateral recessus stenosis, spondylolisthesis, etc., so called ''biradicular syndrome'' should occur. Anomalies of the lumbosacral nerve roots, if not properly recognized, may lead to injury of these nerves during operation of the lumbar spine. Recently, the chance of finding these anomalous roots has been increased more and more with the use of metrizamide myelography and metrizamide CT, because of the improvement of the opacification of nerve roots. We describe the findings of the anomalous roots as revealed by these two methods. They demonstrate two nerve roots running parallel and the asymmetrical wide root sleeve. Under such circumstances, it is important to distinguish the anomalous roots from the normal ventral and dorsal roots. (author)

Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neurons with Proprioceptive Function.

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Hong, Gyu-Sang; Lee, Byeongjun; Wee, Jungwon; Chun, Hyeyeon; Kim, Hyungsup; Jung, Jooyoung; Cha, Joo Young; Riew, Tae-Ryong; Kim, Gyu Hyun; Kim, In-Beom; Oh, Uhtaek

2016-07-06

Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels. Moreover, TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination. Identification of this gene advances our understanding of the various types of mechanosensations, including proprioception. Copyright © 2016 Elsevier Inc. All rights reserved.

RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.

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Caroline Flegel

Full Text Available The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq to conduct the first expression analysis of human trigeminal ganglia (TG and dorsal root ganglia (DRG. We analyzed the data with a focus on G-protein coupled receptors (GPCRs and ion channels, which are (potentially involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues.

Lack of body positional effects on paresthesias when stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain.

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Kramer, Jeffery; Liem, Liong; Russo, Marc; Smet, Iris; Van Buyten, Jean-Pierre; Huygen, Frank

2015-01-01

One prominent side effect from neurostimulation techniques, and in particular spinal cord stimulation (SCS), is the change in intensity of stimulation when moving from an upright (vertical) to a recumbent or supine (horizontal) position and vice versa. It is well understood that the effects of gravity combined with highly conductive cerebrospinal fluid provide the mechanism by which changes in body position can alter the intensity of stimulation-induced paresthesias. While these effects are well established for leads that are placed within the more medial aspects of the spinal canal, little is known about these potential effects in leads placed in the lateral epidural space and in particular within the neural foramina near the dorsal root ganglion (DRG). We prospectively validated a newly developed paresthesia intensity rating scale and compared perceived paresthesia intensities when subjects assumed upright vs. supine bodily positions during neuromodulation of the DRG. On average, the correlation coefficient between stimulation intensity (pulse amplitude) and perceived paresthesia intensity was 0.83, demonstrating a strong linear relationship. No significant differences in paresthesia intensities were reported within subjects when moving from an upright (4.5 ± 0.14) to supine position 4.5 (± 0.12) (p > 0.05). This effect persisted through 12 months following implant. Neuromodulation of the DRG produces paresthesias that remain consistent across body positions, suggesting that this paradigm may be less susceptible to positional effects than dorsal column stimulation. © 2014 International Neuromodulation Society.

Sex differences in pain-related behavior and expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2.

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Ferhatovic, Lejla; Banozic, Adriana; Kostic, Sandra; Sapunar, Damir; Puljak, Livia

2013-06-01

Sex differences in pain-related behavior and expression of calcium/calmodulin dependent protein kinase II (CaMKII) in dorsal root ganglia were studied in rat models of Diabetes mellitus type 1 (DM1) and type 2 (DM2). DM1 was induced with 55mg/kg streptozotocin, and DM2 with a combination of high-fat diet and 35mg/kg of streptozotocin. Pain-related behavior was analyzed using thermal and mechanical stimuli. The expression of CaMKII was analyzed with immunofluorescence. Sexual dimorphism in glycemia, and expression of CaMKII was observed in the rat model of DM1, but not in DM2 animals. Increased expression of total CaMKII (tCaMKII) in small-diameter dorsal root ganglia neurons, which are associated with nociception, was found only in male DM1 rats. None of the animals showed increased expression of the phosphorylated alpha CaMKII isoform in small-diameter neurons. The expression of gamma and delta isoforms of CaMKII remained unchanged in all analyzed animal groups. Different patterns of glycemia and tCaMKII expression in male and female model of DM1 were not associated with sexual dimorphism in pain-related behavior. The present findings do not suggest sex-related differences in diabetic painful peripheral neuropathy in male and female diabetic rats. Copyright © 2012 Elsevier GmbH. All rights reserved.

Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP).

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Eldabe, Sam; Burger, Katja; Moser, Heinrich; Klase, Daniel; Schu, Stefan; Wahlstedt, Anders; Vanderick, Bernard; Francois, Eric; Kramer, Jeffery; Subbaroyan, Jeyakumar

2015-10-01

Phantom limb pain (PLP) is a neuropathic condition in which pain is perceived as arising from an amputated limb. PLP is distinct from, although associated with, pain in the residual limb and nonpainful phantom sensations of the missing limb. Its treatment is extremely challenging; pharmaceutical options, while commonly employed, may be insufficient or intolerable. Neuromodulatory interventions such as spinal cord stimulation have generated mixed results and may be limited by poor somatotopic specificity. It was theorized that dorsal root ganglion (DRG) neuromodulation may be more effective. Patients trialed a DRG neurostimulation system for their PLP and were subsequently implanted if results were positive. Retrospective chart review was completed, including pain ratings on a 100-mm visual analogue scale (VAS) and patient-reported outcomes. Across eight patients, the average baseline pain rating was 85.5 mm. At follow-up (mean of 14.4 months), pain was rated at 43.5 mm. Subjective ratings of quality of life and functional capacity improved. Some patients reduced or eliminated pain medications. Patients reported precise concordance of the paresthesia with painful regions, including in their phantom limbs; in one case, stimulation eliminated PLP as well as nonpainful phantom sensations. Three patients experienced a diminution of pain relief, despite good initial outcomes. DRG neuromodulation may be an effective tool in treating this pain etiology. Clinical outcomes in this report support recent converging evidence suggesting that the DRG may be the site of PLP generation and/or maintenance. Further research is warranted to elucidate mechanisms and optimal treatment pathways. © 2015 International Neuromodulation Society.

Detection of genes regulated by Lmx1b during limb dorsalization.

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Feenstra, Jennifer M; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E; Eppey, Richard J; Oberg, Kerby C

2012-05-01

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

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Leonidas Apostolidis

Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

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Stotz, Stephanie C.; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E.

2008-01-01

Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. PMID:18461159

Dorsal rhizotomy for children with spastic diplegia of cerebral palsy origin: usefulness of intraoperative monitoring.

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Georgoulis, George; Brînzeu, Andrei; Sindou, Marc

2018-04-13

OBJECTIVE The utility of intraoperative neuromonitoring (ION), namely the study of muscle responses to radicular stimulation, remains controversial. The authors performed a prospective study combining ventral root (VR) stimulation for mapping anatomical levels and dorsal root (DR) stimulation as physiological testing of metameric excitability. The purpose was to evaluate to what extent the intraoperative data led to modifications in the initial decisions for surgical sectioning established by the pediatric multidisciplinary team (i.e., preoperative chart), and thus estimate its practical usefulness. METHODS Thirteen children with spastic diplegia underwent the following surgical protocol. First, a bilateral intradural approach was made to the L2-S2 VRs and DRs at the exit from or entry to their respective dural sheaths, through multilevel interlaminar enlarged openings. Second, stimulation-just above the threshold-of the VR at 2 Hz to establish topography of radicular myotome distribution, and then of the DR at 50 Hz as an excitability test of root circuitry, with independent identification of muscle responses by the physiotherapist and by electromyographic recordings. The study aimed to compare the final amounts of root sectioning-per radicular level, established after intraoperative neuromonitoring guidance-with those determined by the multidisciplinary team in the presurgical chart. RESULTS The use of ION resulted in differences in the final percentage of root sectioning for all root levels. The root levels corresponding to the upper lumbar segments were modestly excitable under DR stimulation, whereas progressively lower root levels displayed higher excitability. The difference between root levels was highly significant, as evaluated by electromyography (p = 0.00004) as well as by the physiotherapist (p = 0.00001). Modifications were decided in 11 of the 13 patients (84%), and the mean absolute difference in the percentage of sectioning quantity per radicular

The role of the transcription factor Rbpj in the development of dorsal root ganglia

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Chen Jia-Yin

2011-04-01

Full Text Available Abstract Background The dorsal root ganglion (DRG is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs, and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood. Results In the present study, we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in Rbpj-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of Rbpj conditional knock-out mice. Conclusions Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating NeuroD1 expression, and is required for DRG gliogenesis in vivo.

Effects of 4-phenyl butyric acid on high glucose-induced alterations in dorsal root ganglion neurons.

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Sharma, Dilip; Singh, Jitendra Narain; Sharma, Shyam S

2016-12-02

Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding. 4-phenyl butyric acid (4-PBA) is a potent and selective chemical chaperone; which may inhibit ER stress. It may be hypothesized that 4-PBA could attenuate via channels in DRG in diabetic neuropathy. Effects of 4-PBA were determined by applying different parameters of oxidative stress, cell viability, apoptosis assays and channel expression in cultured DRG neurons. Hyperglycemia-induced apoptosis in the DRG neuron was inhibited by 4-PBA. Cell viability of DRG neurons was not altered by 4-PBA. Oxidative stress was significantly blocked by the 4-PBA. Sodium channel expression was not altered by the 4-PBA. Our data provide evidence that the hyperglycemia-induced alteration may be reduced by the 4-PBA without altering the sodium channel expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis.

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Kent, Alexander R; Min, Xiaoyi; Hogan, Quinn H; Kramer, Jeffery M

2018-04-01

The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing. The transmembrane potential was measured along the neuron to determine the effect of stimulation on intrinsic activity across stimulation parameters, cell location/orientation, and membrane properties. The model was validated by showing close correspondence in action potential (AP) characteristics and firing patterns when compared to experimental measurements. Subsequently, the model output demonstrated that T-junction filtering was amplified with DRG stimulation, thereby blocking afferent signaling, with cathodic stimulation at amplitudes of 2.8-5.5 × stimulation threshold and frequencies above 2 Hz. This amplified filtering was dependent on the presence of calcium and calcium-dependent small-conductance potassium channels, which produced a hyperpolarization offset in the soma, stem, and T-junction with repeated somatic APs during stimulation. Additionally, DRG stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with cathodic or anodic stimulation at amplitudes of 3-11 × threshold and frequencies above 2 Hz. These effects were dependent on the stem axon being relatively close to and oriented toward a stimulating contact. These results align with the working hypotheses on the mechanisms of DRG stimulation, and indicate the importance of stimulation amplitude, polarity, and cell location/orientation on neuronal responses. © 2018 International Neuromodulation Society.

Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

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Stotz, Stephanie C; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E

2008-05-07

Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

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Valentina A Carozzi

Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

Modality-Based Organization of Ascending Somatosensory Axons in the Direct Dorsal Column Pathway

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Niu, Jingwen; Ding, Long; Li, Jian J.; Kim, Hyukmin; Liu, Jiakun; Li, Haipeng; Moberly, Andrew; Badea, Tudor C.; Duncan, Ian D.; Son, Young-Jin; Scherer, Steven S.

2013-01-01

The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the “somatotopic map” model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial–lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough “somatotopic map” was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway. PMID:24198362

Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons.

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Liu, Ting-Ting; Qu, Zu-Wei; Qiu, Chun-Yu; Qiu, Fang; Ren, Cuixia; Gan, Xiong; Peng, Fang; Hu, Wang-Ping

2015-02-01

Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l-THP is poorly understood. This study shows that l-THP can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l-THP dose dependently decreased the amplitude of proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l-THP shifted the proton concentration-response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH0.5 value. Moreover, l-THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l-THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l-THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l-THP. © 2014 Wiley Periodicals, Inc.

Characterization of Na+ and Ca2+ channels in zebrafish dorsal root ganglion neurons.

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Yu-Jin Won

Full Text Available BACKGROUND: Dorsal root ganglia (DRG somata from rodents have provided an excellent model system to study ion channel properties and modulation using electrophysiological investigation. As in other vertebrates, zebrafish (Danio rerio DRG are organized segmentally and possess peripheral axons that bifurcate into each body segment. However, the electrical properties of zebrafish DRG sensory neurons, as compared with their mammalian counterparts, are relatively unexplored because a preparation suitable for electrophysiological studies has not been available. METHODOLOGY/PRINCIPAL FINDINGS: We show enzymatically dissociated DRG neurons from juvenile zebrafish expressing Isl2b-promoter driven EGFP were easily identified with fluorescence microscopy and amenable to conventional whole-cell patch-clamp studies. Two kinetically distinct TTX-sensitive Na(+ currents (rapidly- and slowly-inactivating were discovered. Rapidly-inactivating I(Na were preferentially expressed in relatively large neurons, while slowly-inactivating I(Na was more prevalent in smaller DRG neurons. RT-PCR analysis suggests zscn1aa/ab, zscn8aa/ab, zscn4ab and zscn5Laa are possible candidates for these I(Na components. Voltage-gated Ca(2+ currents (I(Ca were primarily (87% comprised of a high-voltage activated component arising from ω-conotoxin GVIA-sensitive Ca(V2.2 (N-type Ca(2+ channels. A few DRG neurons (8% displayed a miniscule low-voltage-activated component. I(Ca in zebrafish DRG neurons were modulated by neurotransmitters via either voltage-dependent or -independent G-protein signaling pathway with large cell-to-cell response variability. CONCLUSIONS/SIGNIFICANCE: Our present results indicate that, as in higher vertebrates, zebrafish DRG neurons are heterogeneous being composed of functionally distinct subpopulations that may correlate with different sensory modalities. These findings provide the first comparison of zebrafish and rodent DRG neuron electrical properties and

Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

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Stephanie C Stotz

2008-05-01

Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

Purinergic transmission and transglial signaling between neuron somata in the dorsal root ganglion.

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Rozanski, Gabriela M; Li, Qi; Kim, Hyunhee; Stanley, Elise F

2013-02-01

Most dorsal root ganglion neuronal somata (NS) are isolated from their neighbours by a satellite glial cell (SGC) sheath. However, some NS are associated in pairs, separated solely by the membrane septum of a common SGC to form a neuron-glial cell-neuron (NGlN) trimer. We reported that stimulation of one NS evokes a delayed, noisy and long-duration inward current in both itself and its passive partner that was blocked by suramin, a general purinergic antagonist. Here we test the hypothesis that NGlN transmission involves purinergic activation of the SGC. Stimulation of the NS triggered a sustained current noise in the SGC. Block of transmission through the NGlN by reactive blue 2 or thapsigargin, a Ca(2+) store-depletion agent, implicated a Ca(2+) store discharge-linked P2Y receptor. P2Y2 was identified by simulation of the NGlN-like transmission by puffing UTP onto the SGC and by immunocytochemical localization to the SGC membrane septum. Block of the UTP effect by BAPTA, an intracellular Ca(2+) scavenger, supported the involvement of SGC Ca(2+) stores in the signaling pathway. We infer that transmission through the NGlN trimer involves secretion of ATP from the NS and triggering of SGC Ca(2+) store discharge via P2Y2 receptors. Presumably, cytoplasmic Ca(2+) elevation leads to the release of an as-yet unidentified second transmitter from the glial cell to complete transmission. Thus, the two NS of the NGlN trimer communicate via a 'sandwich synapse' transglial pathway, a novel signaling mechanism that may contribute to information transfer in other regions of the nervous system. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

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Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

2009-11-01

Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity.

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Song, Dan-dan; Li, Yong; Tang, Dong; Huang, Li-ya; Yuan, Yao-zong

2014-05-01

Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 μg·kg(-1)·day(-1)). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

Tang-Luo-Ning Improves Mitochondrial Antioxidase Activity in Dorsal Root Ganglia of Diabetic Rats: A Proteomics Study

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Taojing Zhang

2017-01-01

Full Text Available Tang-luo-ning (TLN is a traditional Chinese herbal recipe for treating diabetic peripheral neuropathy (DPN. In this study, we investigated mitochondrial protein profiles in a diabetic rat model and explored the potential protective effect of TLN. Diabetic rats were established by injection of streptozocin (STZ and divided into model, alpha lipoic acid (ALA, and TLN groups. Mitochondrial proteins were isolated from dorsal root ganglia and proteomic analysis was used to quantify the differentially expressed proteins. Tang-luo-ning mitigated STZ-induced diabetic symptoms and blood glucose level, including response time to cold or hot stimulation and nerve conductive velocity. As compared to the normal, there were 388 differentially expressed proteins in the TLN group, 445 in ALA group, and 451 in model group. As compared to the model group, there were 275 differential proteins in TLN group and 251 in ALA group. As compared to model group, mitochondrial complex III was significantly decreased, while glutathione peroxidase and peroxidase were increased in TLN group. When compared with ALA group, the mitochondrial complex III was increased, and mitochondrial complex IV was decreased in TLN group. Together, TLN should have a strong antioxidative activity, which appears to be modulated through regulation of respiratory complexes and antioxidases.

FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum.

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Satoh, Akira; Makanae, Aki; Nishimoto, Yurie; Mitogawa, Kazumasa

2016-09-01

Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration. To gather experimental evidence, the technical difficulties involved in the usage of axolotls had to be overcome. We achieved this by modifying the electroporation method. When Fgf8-AcGFP or Bmp7-AcGFP was electroporated into the axolotl dorsal root ganglia (DRG), GFP signals were detectable in the regenerating limb region. This suggested that Fgf8 and Bmp7 synthesized in neural cells in the DRG were delivered to the limbs through the long axons. Further knockdown experiments with double-stranded RNA interference resulted in impaired limb regeneration ability. These results strongly suggest that Fgf and Bmp are the major neural inputs that control the organ regeneration ability. Copyright © 2016 Elsevier Inc. All rights reserved.

Oil Red O and Hematoxylin and Eosin Staining for Quantification of Atherosclerosis Burden in Mouse Aorta and Aortic Root.

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Andrés-Manzano, M Jesús; Andrés, Vicente; Dorado, Beatriz

2015-01-01

Methods for staining tissues with Oil Red O and hematoxylin-eosin are classical histological techniques that are widely used to quantify atherosclerotic burden in mouse tissues because of their ease of use, reliability, and the large amount of information they provide. These stains can provide quantitative data about the impact of a genetic or environmental factor on atherosclerotic burden and on the initiation, progression, or regression of the disease, and can also be used to evaluate the efficacy of drugs designed to prevent or treat atherosclerosis. This chapter provides protocols for quantifying atherosclerotic burden in mouse aorta and aortic root, including methods for dissection, Oil Red O staining, hematoxylin-eosin staining, and image analysis.

The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel.

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Iftinca, Mircea; Flynn, Robyn; Basso, Lilian; Melo, Helvira; Aboushousha, Reem; Taylor, Lauren; Altier, Christophe

2016-01-01

Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund's Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund's Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. Our work identified Hsc70 and its ATPase activity as a central cofactor of TRPV1 channel function

Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain.

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A K Reinhold

Full Text Available Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS. Two fluorescent tracers, Fluoroemerald (FE and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI, were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropin-releasing hormone (CRH, providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG.

Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

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David L García-Ramírez

Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

Expression profile of vesicular nucleotide transporter (VNUT, SLC17A9) in subpopulations of rat dorsal root ganglion neurons.

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Nishida, Kentaro; Nomura, Yuka; Kawamori, Kanako; Moriyama, Yoshinori; Nagasawa, Kazuki

2014-09-05

ATP plays an important role in the signal transduction between sensory neurons and satellite cells in dorsal root ganglia (DRGs). In primary cultured DRG neurons, ATP is known to be stored in lysosomes via a vesicular nucleotide transporter (VNUT), and to be released into the intercellular space through exocytosis. DRGs consist of large-, medium- and small-sized neurons, which play different roles in sensory transmission, but there is no information on the expression profiles of VNUT in DRG subpopulations. Here, we obtained detailed expression profiles of VNUT in isolated rat DRG tissues. On immunohistochemical analysis, VNUT was found in DRG neurons, and was predominantly expressed by the small- and medium-sized DRG ones, as judged upon visual inspection, and this was compatible with the finding that the number of VNUT-positive DRG neurons in IB4-positive cells was greater than that in NF200-positive ones. These results suggest that VNUT play a role in ATP accumulation in DRG neurons, especially in small- and medium-sized ones, and might be involved in ATP-mediated nociceptive signaling in DRGs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

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Su Lin

2011-11-01

Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

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Andrea Forero

2017-09-01

Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

Science.gov (United States)

Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

2017-11-01

Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is

Zinc-enriched (ZEN) terminals in mouse spinal cord

DEFF Research Database (Denmark)

Jo, S M; Danscher, G; Schrøder, H D

2000-01-01

The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the Zn...... dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord....

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

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van Rhijn Lodewijk W

2010-06-01

Full Text Available Abstract Background Cerebral palsy (CP may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. Methods We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS, Gross Motor Function Measure (GMFM and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS for spasticity, pain and ease of care. Results A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. Conclusion RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial.

Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express connexin 36.

Science.gov (United States)

Pérez Armendariz, E Martha; Norcini, Monica; Hernández-Tellez, Beatriz; Castell-Rodríguez, Andrés; Coronel-Cruz, Cristina; Alquicira, Raquel Guerrero; Sideris, Alexandra; Recio-Pinto, Esperanza

2018-04-01

Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF). Double staining revealed that Cx36 co-localizes with both anti-β-III tubulin, a neuronal marker, and anti-glutamine synthetase, a satellite glial cell (SGC) marker. In neurons, Cx36 staining was mostly uniform in somata and fibers of all sizes and its intensity increased at the cell membranes. This labeling pattern was in contrast with Cx36 IF dots mainly found at junctional membranes in islet beta cells used as a control tissue. Co-staining with anti-Cx43 and anti-Cx36 showed that whereas mostly uniform staining of Cx36 was found throughout neurons and SGCs, Cx43 IF puncta were localized to SGCs. Cx36 mRNA was expressed in normal lumbar DRG, and it was significantly down-regulated in L4 DRG of rats that underwent sciatic nerve injury resulting in persistent hypersensitivity. Collectively, these findings demonstrated that neurons and SGCs express Cx36 protein in normal DRG, and suggested that perturbation of Cx36 levels may contribute to chronic neuropathic pain resulting from a peripheral nerve injury. Copyright © 2017 Elsevier GmbH. All rights reserved.

Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

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Kerui Gong

Full Text Available Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG one week following a chronic constriction injury (CCI of the sciatic nerve in adult rats. We found that small diameter DRG neurons (30 µm were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA and kainic acid (KA, or the group I metabotropic receptor (mGluR agonist (S-3,5-dihydroxyphenylglycine (DHPG, induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study.

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Sundt, Danielle; Gamper, Nikita; Jaffe, David B

2015-12-01

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na(+) channels. A model containing only fast voltage-gated Na(+) and delayed-rectifier K(+) channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca(2+)-dependent K(+) current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na(+)-K(+) pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca(2+)-dependent K(+) current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. Copyright © 2015 the American Physiological Society.

First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model.

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Turkmenoglu, Osman N; Kanat, Ayhan; Yolas, Coskun; Aydin, Mehmet Dumlu; Ezirmik, Naci; Gundogdu, Cemal

2017-01-01

The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH ( n = 8), serum saline (SS) (SS; n = 6) and control ( n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. The mean alive neuron density of the L4DRG was 15420 ± 1240/mm 3 and degenerated neuron density was 1045 ± 260/mm 3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm 3 and 1365 ± 480/mm 3 in serum saline (SS), 9845 ± 1028/mm 3 and 4560 ± 1340/mm 3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm 3 in the control group and 1,030 ± 0,240 mm 3 in the SF group and 0,910 ± 0,170 mm 3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups ( P < 0.05). Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

Science.gov (United States)

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

Effects of (−-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons

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Jian-Min Jiang

2013-05-01

Full Text Available The (−-gallocatechin-3-gallate (GCG concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent.

Effect of ginseng root polysaccharides on cutaneous wound repair in ...

African Journals Online (AJOL)

with WGP (15 mg or 30 mg) or mouse epidermal growth factor (mEGF, 0.1 mL, 2000 IU/mL), respectively. .... dorsal hair was clipped, and one full-thickness, round wound ..... Aloe vera induce MMP-3 and TIMP-2 gene expression during the ...

PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion.

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Li, Li; Zhao, Lei; Wang, Yang; Ma, Ke-tao; Shi, Wen-yan; Wang, Ying-zi; Si, Jun-qiang

2015-02-01

The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

Low voltage-activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse.

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Rozanski, Gabriela M; Nath, Arup R; Adams, Michael E; Stanley, Elise F

2013-11-15

A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin satellite glial cell membrane septa. Stimulation of one neuron leads to transglial activation of its pair by a bi-, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca(2+) entry via voltage-gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (-50 mV) or low-concentration Ni(2+) (0.1 mM). Transmission persisted using a voltage pulse to -40 mV from a holding potential of -80 mV, confirming the involvement of a low voltage-activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation- and Ni(2+)-sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter-somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub-threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.

Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication.

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Rozanski, Gabriela M; Li, Qi; Stanley, Elise F

2013-04-01

The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS-glial cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transglial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 receptor. Isolated DRG cell clusters exhibited daisy-chain and branching NS-glial cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the glial-to-neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

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Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting

2016-10-05

An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

Creating a Strain Relief Loop during S1 Transforaminal Lead Placement for Dorsal Root Ganglion Stimulation for Foot Pain: A Technical Note.

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van Velsen, Valery; van Helmond, Noud; Chapman, Kenneth B

2018-04-01

Chronic neuropathic pain is often refractory to conventional medical treatments and leads to significant disability and socio-economic burden. Dorsal root ganglion (DRG) stimulation has recently emerged as a treatment for persistent neuropathic pain, but creating a strain relief loop at the S1 level has thus far been a challenging technical component of DRG lead placement. We describe a refined technique for strain relief loop formation at the S1 level using a transforaminal approach that we employed in a 45-year-old patient with intractable foot pain. We successfully placed a strain relief loop in the sacral space in a predictable and easily reproducible manner using a transforaminal anchorless approach. The patient experienced a decrease in visual analog pain score (85%), and improvement in function during the trial period, and proceeded with permanent implantation. The described sacral transforaminal strain relief loop formation technique appears to be a more reliable and predictable technique of DRG lead placement in the sacrum than those previously documented. © 2017 World Institute of Pain.

Accurate assessment of in situ isometric contractile properties of hindlimb plantar and dorsal flexor muscle complex of intact mice

NARCIS (Netherlands)

Gorselink, M.; Drost, M.R.; Louw, de J.; Willems, P.J.B.; Rosielle, P.C.J.N.; Janssen, J.D.; Vusse, van der G.J.

2000-01-01

An isometric torque sensor for measuring in situ contractions of plantar or dorsal flexors of intact mouse hindlimb has been developed and evaluated. With this device, muscle torque can be accurately measured within the range of -14 mN·m to +14 mN·m. Special attention was paid to fixation of the

Immunostaining for Homer reveals the majority of excitatory synapses in laminae I?III of the mouse spinal dorsal horn

OpenAIRE

Gutierrez-Mecinas, Maria; Kuehn, Emily D.; Abraira, Victoria E.; Polg?r, Erika; Watanabe, Masahiko; Todd, Andrew J.

2016-01-01

The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I–III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty i...

Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

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Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

2018-05-05

Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Dorsal skinfold chamber models in mice

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Schreiter, Jeannine

2017-07-01

Full Text Available Background/purpose: The use of dorsal skinfold chamber models has substantially improved the understanding of micro-vascularisation in pathophysiology over the last eight decades. It allows pathophysiological studies of vascularisation over a continuous period of time. The dorsal skinfold chamber is an attractive technique for monitoring the vascularisation of autologous or allogenic transplants, wound healing, tumorigenesis and compatibility of biomaterial implants. To further reduce the animals’ discomfort while carrying the dorsal skinfold chamber, we developed a smaller chamber (the Leipzig Dorsal Skinfold Chamber and summarized the commercial available chamber models. In addition we compared our model to the common chamber. Methods: The Leipzig Dorsal Skinfold Chamber was applied to female mice with a mean weight of 22 g. Angiogenesis within the dorsal skinfold chamber was evaluated after injection of fluorescein isothiocyanate dextran with an Axio Scope microscope. The mean vessel density within the dorsal skinfold chamber was assessed over a period of 21 days at five different time points. The gained data were compared to previous results using a bigger and heavier dorsal skinfold model in mice. A PubMed and a patent search were performed and all papers related to “dorsal skinfold chamber” from 1 of January 2006 to 31 of December 2015 were evaluated regarding the dorsal skinfold chamber models and their technical improvements. The main models are described and compared to our titanium Leipzig Dorsal Skinfold Chamber model.Results: The Leipzig Dorsal Skinfold Chamber fulfils all requirements of continuous models known from previous chamber models while reducing irritation to the mice. Five different chamber models have been identified showing substantial regional diversity. The newly elaborated titanium dorsal skinfold chamber may replace the pre-existing titanium chamber model used in Germany so far, as it is smaller and lighter

Spinal dorsal horn astrocytes: New players in chronic itch

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Makoto Tsuda

2017-01-01

Full Text Available Chronic itch is a debilitating symptom of inflammatory skin conditions, such as atopic dermatitis, and systemic diseases, for which existing treatment is largely ineffective. Recent studies have revealed the selective neuronal pathways that are involved in itch sensations; however, the mechanisms by which itch turns into a pathological chronic state are poorly understood. Recent advances in our understanding of the mechanisms producing chronic itch have been made by defining causal roles for astrocytes in the spinal dorsal horn in mouse models of chronic itch including atopic dermatitis. Understanding the key roles of astrocytes may provide us with exciting insights into the mechanisms for itch chronicity and lead to a previously unrecognized target for treating chronic itch.

Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury.

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Mannion James W

2002-10-01

Full Text Available Abstract Background Rat oligonucleotide microarrays were used to detect changes in gene expression in the dorsal root ganglion (DRG 3 days following sciatic nerve transection (axotomy. Two comparisons were made using two sets of triplicate microarrays, naïve versus naïve and naïve versus axotomy. Results Microarray variability was assessed using the naïve versus naïve comparison. These results support use of a P 1.5-fold expression change and P 1.5-fold and P in situ hybridization verified the expression of 24 transcripts. These data showed an 83% concordance rate with the arrays; most mismatches represent genes with low expression levels reflecting limits of array sensitivity. A significant correlation was found between actual mRNA differences and relative changes between microarrays (r2 = 0.8567. Temporal patterns of individual genes regulation varied. Conclusions We identify parameters for microarray analysis which reduce error while identifying many putatively regulated genes. Functional classification of these genes suggest reorganization of cell structural components, activation of genes expressed by immune and inflammatory cells and down-regulation of genes involved in neurotransmission.

Histology study on the dorsal root ganglia of rats with 125I seed brachytherapy at intervertebral foramen

International Nuclear Information System (INIS)

Zhang Wenyi; Wang Huixing; Ding Yanqiu; Qu Ximei; Wang Liqin; Liu Zhongchao; Cui Songye; Jiao Ling

2012-01-01

Objective: To investigate the effect of the histological changes on rat dorsal root ganglia (DRG) after 125 I seed brachytherapy.Methods Twelve adult male Sprague-Dawley rats (150-180 g each) were randomly divided into 6 groups, 125 I seeds with different activities of 0 (Titanium shell), 14.8, 18.5, 22.2, 25.9 and 29.6 MBq were implanted to 6 groups of rats respectively and the behavioral changes of rats were observed. The rats were killed in different periods after implantation,the morphological changes in DRG and surrounding muscle tissue were observed with an Olympus BX51 optical microscope and then the irradiation doses were estimated. Results: After 125 I seed implantation, the movement function of rats was not affected and the weight of rats gained after 7 days. After the titanium shell implantation, very few mild swelling was induced in neuroganglion cells that still had clear nucleolus and normal cytoplasm. At 14 days after 18.5 MBq seed implantation, cell swelling was more serious and cell dehydrating, nuclear condensation and nuclear fragmentation appeared after 30 days. At 60 days after 29.6 MBq of seed implantation, nuclear dissolution and cytoplasmic shrinkage were induced in a large number of cells.In general, the severity of fibrosis was aggravated with the time post-irradiation and the dose in the muscles around the ganglion. Conclusions: After 125 I seed implantation,the injury degree of DRG tissue is dose-dependent, and the 125 I seed irradiation would have analgesic effect on releasing intractable pain. (authors)

Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

Science.gov (United States)

Chang, Ming-Fong; Hsieh, Jung-Hsien; Chiang, Hao; Kan, Hung-Wei; Huang, Cho-Min; Chellis, Luke; Lin, Bo-Shiou; Miaw, Shi-Chuen; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

2016-01-01

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection. PMID:27748450

Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.

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Haro, Endika; Watson, Billy A; Feenstra, Jennifer M; Tegeler, Luke; Pira, Charmaine U; Mohan, Subburaman; Oberg, Kerby C

2017-06-01

Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed by next-generation sequencing (ChIP-seq). Nearly 84% ( n =617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis -regulatory modules (PCRMs). In addition, 73 LBIs mapped to CRMs that are known to be active during limb development. We compared Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization. © 2017. Published by The Company of Biologists Ltd.

Crucial roles of NGF in dorsal horn plasticity in partially deafferentated cats.

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Liu, Jia; Chen, Shan-Shan; Dan, Qi-Qin; Rong, Rong; Zhou, Xue; Zhang, Lian-Feng; Wang, Ting-Hua

2011-04-01

Though exogenous nerve growth factor (NGF) has been implicated in spinal cord plasticity, whether endogenous NGF plays a crucial role has not been established in vivo. This study investigated first the role of endogenous NGF in spinal dorsal horn (DH) plasticity following removal of L1-L5 and L7-S2 dorsal root ganglions (DRGs) in cats. Co-culture of chick embryo DRG with DH condition media, protein band fishing by cells as well as western blot showed that NGF could promote neurite growth in vitro. Immunohistochemistry and in situ hybridization technique revealed an increase in the NGF and NGF mRNA immunoreactive cells in the DH after partial deafferentation. Lastly, after blocking with NGF antibody, choleragen subunit B horseradish peroxidase (CB-HRP) tracing showed a reduction in the neuronal sprouting observed in the DH. Our results demonstrated that in the cat, endogenous NGF plays a crucial role in DH plasticity after partial deafferentation.

Automated Root Tracking with "Root System Analyzer"

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Schnepf, Andrea; Jin, Meina; Ockert, Charlotte; Bol, Roland; Leitner, Daniel

2015-04-01

Crucial factors for plant development are water and nutrient availability in soils. Thus, root architecture is a main aspect of plant productivity and needs to be accurately considered when describing root processes. Images of root architecture contain a huge amount of information, and image analysis helps to recover parameters describing certain root architectural and morphological traits. The majority of imaging systems for root systems are designed for two-dimensional images, such as RootReader2, GiA Roots, SmartRoot, EZ-Rhizo, and Growscreen, but most of them are semi-automated and involve mouse-clicks in each root by the user. "Root System Analyzer" is a new, fully automated approach for recovering root architectural parameters from two-dimensional images of root systems. Individual roots can still be corrected manually in a user interface if required. The algorithm starts with a sequence of segmented two-dimensional images showing the dynamic development of a root system. For each image, morphological operators are used for skeletonization. Based on this, a graph representation of the root system is created. A dynamic root architecture model helps to determine which edges of the graph belong to an individual root. The algorithm elongates each root at the root tip and simulates growth confined within the already existing graph representation. The increment of root elongation is calculated assuming constant growth. For each root, the algorithm finds all possible paths and elongates the root in the direction of the optimal path. In this way, each edge of the graph is assigned to one or more coherent roots. Image sequences of root systems are handled in such a way that the previous image is used as a starting point for the current image. The algorithm is implemented in a set of Matlab m-files. Output of Root System Analyzer is a data structure that includes for each root an identification number, the branching order, the time of emergence, the parent

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach

OpenAIRE

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D. K.; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as ...

Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain.

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Meng, Bo; Shen, Lu-Lu; Shi, Xiao-Ting; Gong, Yong-Sheng; Fan, Xiao-Fang; Li, Jun; Cao, Hong

2015-09-25

Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Versatility of the ventral approach in bulbar urethroplasty using dorsal, ventral or dorsal plus ventral oral grafts.

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Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; De Nunzio, Cosimo; Giannitsas, Kostas; Shokeir, Ahmed A

2012-06-01

To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2 cm, range 1.5-5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture 3.7, range 1.5-8) a ventral graft urethroplasty (VGU), and 63 (29.2%; mean stricture 3.4, range 1.5-10) a dorsal plus ventral graft urethroplasty (DVGU). The strictured urethra was opened by a ventral-sagittal urethrotomy and BM graft was inserted dorsally or ventrally or dorsal plus ventral to augment the urethral plate. The median follow-up was 37 months. The overall 5-year actuarial success rate was 91.4%. The 5-year actuarial success rates were 87.8%, 95.5% and 86.3% for the DGU, VGU and DVGU, respectively. There were no statistically significant differences among the three groups. Success rates decreased significantly only with a stricture length of >4 cm. In BM graft bulbar urethroplasties the ventral urethrotomy access is simple and versatile, allowing an intraoperative choice of dorsal, ventral or combined dorsal and ventral grafting, with comparable success rates.

High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury.

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Murali, Swetha S; Napier, Ian A; Mohammadi, Sarasa A; Alewood, Paul F; Lewis, Richard J; Christie, MacDonald J

2015-03-01

Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8- to 11-wk-old males (n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium- to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The α2δ-1 subunit was upregulated by 1.7-fold and γ-3, γ-2, and β-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium- to large-diameter neurons. Copyright © 2015 the American Physiological Society.

Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

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Huang Li-Yen

2007-08-01

Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

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Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

Upregulation of EMMPRIN (OX47 in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

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Qun Wang

2015-01-01

Full Text Available Matrix metalloproteinases (MMPs are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR, and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord

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Guiqin Zhu

2016-01-01

Full Text Available Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI in rat tibia (TCI cancer pain model. Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy. Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

P2X₇ receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

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Liu, Shuangmei; Shi, Qingming; Zhu, Qicheng; Zou, Ting; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Wu, Qin; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Lv, Qiulan; Zou, Lifang; Zhang, Xi; Ying, Mofeng; Li, Guodong; Liang, Shangdong

2015-06-01

Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor.

The dorsal shell wall structure of Mesozoic ammonoids

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Gregor Radtke

2017-03-01

Full Text Available The study of pristine preserved shells of Mesozoic Ammonoidea shows different types of construction and formation of the dorsal shell wall. We observe three major types: (i The vast majority of Ammonoidea, usually planispirally coiled, has a prismatic reduced dorsal shell wall which consists of an outer organic component (e.g., wrinkle layer, which is the first layer to be formed, and the subsequently formed dorsal inner prismatic layer. The dorsal mantle tissue suppresses the formation of the outer prismatic layer and nacreous layer. With the exception of the outer organic component, secretion of a shell wall is omitted at the aperture. A prismatic reduced dorsal shell wall is always secreted immediately after the hatching during early teleoconch formation. Due to its broad distribution in (planispiral Ammonoidea, the prismatic reduced dorsal shell wall is probably the general state. (ii Some planispirally coiled Ammonoidea have a nacreous reduced dorsal shell wall which consists of three mineralized layers: two prismatic layers (primary and secondary dorsal inner prismatic layer and an enclosed nacreous layer (secondary dorsal nacreous layer. The dorsal shell wall is omitted at the aperture and was secreted in the rear living chamber. Its layers are a continuation of an umbilical shell doubling (reinforcement by additional shell layers that extends towards the ventral crest of the preceding whorl. The nacreous reduced dorsal shell wall is formed in the process of ontogeny following a prismatic reduced dorsal shell wall. (iii Heteromorph and some planispirally coiled taxa secrete a complete dorsal shell wall which forms a continuation of the ventral and lateral shell layers. It is formed during ontogeny following a prismatic reduced dorsal shell wall or a priori. The construction is identical with the ventral and lateral shell wall, including a dorsal nacreous layer. The wide distribution of the ability to form dorsal nacre indicates that it is

Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

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Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

2017-03-01

The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

Radiographic Outcomes of Dorsal Distraction Distal Radius Plating for Fractures With Dorsal Marginal Impaction.

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Huish, Eric G; Coury, John G; Ibrahim, Mohamed A; Trzeciak, Marc A

2017-04-01

The purpose of this study is to compare radiographic outcomes of patients treated with dorsal spanning plates with previously reported normal values of radiographic distal radius anatomy and compare the results with prior publications for both external fixation and internal fixation with volar locked plates. Patients with complex distal radius fractures including dorsal marginal impaction pattern necessitating dorsal distraction plating at the discretion of the senior authors (M.A.T. and M.A.I.) from May 30, 2013, to December 29, 2015, were identified and included in the study. Retrospective chart and radiograph review was performed on 19 patients, 11 male and 8 female, with mean age of 47.83 years (22-82). No patients were excluded from the study. All fractures united prior to plate removal. The average time the plate was in place was 80.5 days (49-129). Follow-up radiographs showed average radial inclination of 20.5° (13.2°-25.5°), radial height of 10.7 mm (7.5-14 mm), ulnar variance of -0.3 mm (-2.1 to 3.1 mm), and volar tilt of 7.9° (-3° to 15°). One patient had intra-articular step-off greater than 2 mm. Dorsal distraction plating of complex distal radius fractures yields good radiographic results with minimal complications. In cases of complex distal radius fractures including dorsal marginal impaction where volar plating is not considered adequate, a dorsal distraction plate should be considered as an alternative to external fixation due to reduced risk for infection and better control of volar tilt.

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

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Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Different forms of glycine- and GABAA-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons

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Brichta Alan M

2009-11-01

Full Text Available Abstract Background Neurons in superficial (SDH and deep (DDH laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine- (GlyR and GABAA-receptors (GABAARs contribute to fast synaptic inhibition. For rat, several types of GABAAR coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood. Methods and Results Here we compare fast inhibitory synaptic transmission in mouse (P17-37 SDH and DDH using patch-clamp electrophysiology in transverse spinal cord slices (L3-L5 segments, 23°C. GlyR-mediated mIPSCs were detected in 74% (25/34 and 94% (25/27 of SDH and DDH neurons, respectively. In contrast, GABAAR-mediated mIPSCs were detected in virtually all neurons in both regions (93%, 14/15 and 100%, 18/18. Several Gly- and GABAAR properties also differed in SDH vs. DDH. GlyR-mediated mIPSC amplitude was smaller (37.1 ± 3.9 vs. 64.7 ± 5.0 pA; n = 25 each, decay time was slower (8.5 ± 0.8 vs. 5.5 ± 0.3 ms, and frequency was lower (0.15 ± 0.03 vs. 0.72 ± 0.13 Hz in SDH vs. DDH neurons. In contrast, GABAAR-mediated mIPSCs had similar amplitudes (25.6 ± 2.4, n = 14 vs. 25. ± 2.0 pA, n = 18 and frequencies (0.21 ± 0.08 vs. 0.18 ± 0.04 Hz in both regions; however, decay times were slower (23.0 ± 3.2 vs. 18.9 ± 1.8 ms in SDH neurons. Mean single channel conductance underlying mIPSCs was identical for GlyRs (54.3 ± 1.6 pS, n = 11 vs. 55.7 ± 1.8, n = 8 and GABAARs (22.7 ± 1.7 pS, n = 10 vs. 22.4 ± 2.0 pS, n = 11 in both regions. We also tested whether the synthetic endocanabinoid, methandamide (methAEA, had direct effects on Gly- and GABAARs in each spinal cord region. MethAEA (5 μM reduced GlyR-mediated mIPSC frequency in SDH

Hair Growth Promotant Activity of Petroleum Ether Root Extract of ...

African Journals Online (AJOL)

Purpose: To investigate the effect of Glycyrrhiza glabra root extract on hair growth in female Wistar rats. Methods: Female Wistar rats were used for the hair growth promotion studies. They were divided into three groups(n = 6) and their dorsal skin was completely denuded to completely remove hair. Paraffin oil (control), 2 ...

Pulsed Radiofrequency of Dorsal Root Ganglia for the Treatment of Complex Regional Pain Syndrome in an Adolescent with Poliomyelitis Sequel: A Case Report.

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Apiliogullari, Seza; Aydin, Bahattin Kerem; Onal, Ozkan; Kirac, Yunus; Celik, Jale Bengi

2015-07-01

Complex regional pain syndrome (CRPS) is a painful and disabling syndrome in which the patient presents with neuropathic pain, edema, or vasomotor or pseudomotor abnormalities that are often refractory to treatment. Polio paralysis is caused by the damage or destruction of motor neurons in the spine, which lead to corresponding muscle paralysis. This report is a case report on the application of a pulsed radiofrequency (PRF) current to dorsal root ganglia (DRG) for the treatment of CRPS type 1 in an adolescent patient. Single case report. Selcuk University Hospital. A 16-year-old girl who suffered from CRPS type 1 secondary to surgeries for the sequelae of poliomyelitis. PRF current application to the lumbar 4 and lumbar 5 DRG. Pain reduction. The patient had complete resolution of her symptoms, which was maintained at a 6-month follow-up. This case illustrates that PRF applied to lumbar 4 and lumbar 5 DRG may play a significant role in CRPS type 1 management after the surgical treatment of poliomyelitis sequelae in adolescent patients. Further randomized, controlled studies are needed to support this argument. Wiley Periodicals, Inc.

Distinct populations of GABAergic neurons in mouse rhombomere 1 express but do not require the homeodomain transcription factor PITX2.

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Waite, Mindy R; Skaggs, Kaia; Kaviany, Parisa; Skidmore, Jennifer M; Causeret, Frédéric; Martin, James F; Martin, Donna M

2012-01-01

Hindbrain rhombomere 1 (r1) is located caudal to the isthmus, a critical organizer region, and rostral to rhombomere 2 in the developing mouse brain. Dorsal r1 gives rise to the cerebellum, locus coeruleus, and several brainstem nuclei, whereas cells from ventral r1 contribute to the trochlear and trigeminal nuclei as well as serotonergic and GABAergic neurons of the dorsal raphe. Recent studies have identified several molecular events controlling dorsal r1 development. In contrast, very little is known about ventral r1 gene expression and the genetic mechanisms regulating its formation. Neurons with distinct neurotransmitter phenotypes have been identified in ventral r1 including GABAergic, serotonergic, and cholinergic neurons. Here we show that PITX2 marks a distinct population of GABAergic neurons in mouse embryonic ventral r1. This population appears to retain its GABAergic identity even in the absence of PITX2. We provide a comprehensive map of markers that places these PITX2-positive GABAergic neurons in a region of r1 that intersects and is potentially in communication with the dorsal raphe. Copyright © 2011 Elsevier Inc. All rights reserved.

Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis

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Lian, Yu-Ling; Cheng, Ming-Jun; Zhang, Xian-Xia; Wang, Li

2017-01-01

Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto-transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail-flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene-related peptide (CGRP) in L1-L6 DRG was measured via immunohistochemistry, western blotting and RT-qPCR. The results indicated that the Model group exhibited a significant decrease in tail flick latency compared to pre-surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1-L6 DRG significantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1-L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain. PMID:28627595

Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

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Thanawath R Na Phuket

2009-07-01

Full Text Available The dorsal root ganglion (DRG contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling.  Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways

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Paciorkowski, Alex R.; Traylor, Ryan N.; Rosenfeld, Jill A.; Hoover, Jacqueline M.; Harris, Catharine J.; Winter, Susan; Lacassie, Yves; Bialer, Martin; Lamb, Allen N.; Schultz, Roger A.; Berry-Kravis, Elizabeth; Porter, Brenda E.; Falk, Marni; Venkat, Anu; Vanzo, Rena J.; Cohen, Julie S.; Fatemi, Ali; Dobyns, William B.; Shaffer, Lisa G.; Ballif, Blake C.; Marsh, Eric D.

2013-01-01

MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types. PMID:23389741

Dorsal onlay (Barbagli technique) versus dorsal inlay (Asopa technique) buccal mucosal graft urethroplasty for anterior urethral stricture: a prospective randomized study.

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Aldaqadossi, Hussein; El Gamal, Samir; El-Nadey, Mohamed; El Gamal, Osama; Radwan, Mohamed; Gaber, Mohamed

2014-02-01

To compare both the dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa for the management of long anterior urethral stricture. From January 2010 to May 2012, a total of 47 patients with long anterior urethral strictures were randomized into two groups. The first group included 25 patients who were managed by dorsal onlay buccal mucosal graft urethroplasty. The second group included 22 patients who were managed by dorsal inlay buccal mucosal graft urethroplasty. Different clinical parameters, postoperative complications and success rates were compared between both groups. The overall success rate in the dorsal onlay group was 88%, whereas in the dorsal inlay group the success rate was 86.4% during the follow-up period. The mean operative time was significantly longer in the dorsal onlay urethroplasty group (205 ± 19.63 min) than in the dorsal inlay urethroplasty group (128 ± 4.9 min, P-value <0.0001). The average blood loss was significantly higher in the dorsal onlay urethroplasty group (228 ± 5.32 mL) than in the dorsal inlay urethroplasty group (105 ± 12.05 mL, P-value <0.0001). The dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa buccal mucosal graft urethroplasty provide similar success rates. The Asopa technique is easy to carry out, provides shorter operative time and less blood loss, and it is associated with fewer complications for anterior urethral stricture repair. © 2013 The Japanese Urological Association.

Lectin Ulex europaeus agglutinin I specifically labels a subset of primary afferent fibers which project selectively to the superficial dorsal horn of the spinal cord.

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Mori, K

1986-02-19

To examine differential carbohydrate expression among different subsets of primary afferent fibers, several fluorescein-isothiocyanate conjugated lectins were used in a histochemical study of the dorsal root ganglion (DRG) and spinal cord of the rabbit. The lectin Ulex europaeus agglutinin I specifically labeled a subset of DRG cells and primary afferent fibers which projected to the superficial laminae of the dorsal horn. These results suggest that specific carbohydrates containing L-fucosyl residue is expressed selectively in small diameter primary afferent fibers which subserve nociception or thermoception.

Up-regulation of p55 TNF alpha-receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats.

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Sakuma, Yoshihiro; Ohtori, Seiji; Miyagi, Masayuki; Ishikawa, Tetsu; Inoue, Gen; Doya, Hideo; Koshi, Takana; Ito, Toshinori; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Munetaka; Moriya, Hideshige; Takahashi, Kazuhisa

2007-08-01

The rat L5/6 facet joint is multisegmentally innervated from the L1 to L6 dorsal root ganglia (DRG). Tumor necrosis factor (TNF) is a known mediator of inflammation. It has been reported that satellite cells are activated, produce TNF and surround DRG neurons innervating L5/6 facet joints after facet injury. In the current study, changes in TNF receptor (p55) expression in DRG neurons innervating the L5/6 facet joint following facet joint injury were investigated in rats using a retrograde neurotransport method followed by immunohistochemistry. Twenty rats were used for this study. Two crystals of Fluorogold (FG; neurotracer) were applied into the L5/6 facet joint. Seven days after surgery, the dorsal portion of the capsule was cut in the injured group (injured group n = 10). No injury was performed in the non-injured group (n = 10). Fourteen days after the first application of FG, bilateral DRGs from T13 to L6 levels were resected and sectioned. They were subsequently processed for p55 immunohistochemistry. The number of FG labeled neurons and number of FG labeled p55-immunoreactive (IR) neurons were counted. FG labeled DRG neurons innervating the L5/6 facet joint were distributed from ipsilateral L1 to L6 levels. Of FG labeled neurons, the ratio of DRG neurons immunoreactive for p55 in the injured group (50%) was significantly higher than that in the non-injured group (13%). The ratio of p55-IR neurons of FG labeled DRG neurons was significantly higher in total L1 and L2 DRGs than that in total L3, 4, 5 and 6 DRGs in the injured group (L1 and 2 DRG, 67%; L3, 4, 5 and 6 DRG, 37%, percentages of the total number of p55-IR neurons at L1 and L2 level or L3-6 level/the total number of FG-labeled neurons at L1 and L2 level or L3-6 level). These data suggest that up-regulation of p55 in DRG neurons may be involved in the sensory transmission from facet joint injury. Regulation of p55 in DRG neurons innervating the facet joint was different between upper DRG innervated

Quantitative Analysis of Rat Dorsal Root Ganglion Neurons Cultured on Microelectrode Arrays Based on Fluorescence Microscopy Image Processing.

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Mari, João Fernando; Saito, José Hiroki; Neves, Amanda Ferreira; Lotufo, Celina Monteiro da Cruz; Destro-Filho, João-Batista; Nicoletti, Maria do Carmo

2015-12-01

Microelectrode Arrays (MEA) are devices for long term electrophysiological recording of extracellular spontaneous or evocated activities on in vitro neuron culture. This work proposes and develops a framework for quantitative and morphological analysis of neuron cultures on MEAs, by processing their corresponding images, acquired by fluorescence microscopy. The neurons are segmented from the fluorescence channel images using a combination of segmentation by thresholding, watershed transform, and object classification. The positioning of microelectrodes is obtained from the transmitted light channel images using the circular Hough transform. The proposed method was applied to images of dissociated culture of rat dorsal root ganglion (DRG) neuronal cells. The morphological and topological quantitative analysis carried out produced information regarding the state of culture, such as population count, neuron-to-neuron and neuron-to-microelectrode distances, soma morphologies, neuron sizes, neuron and microelectrode spatial distributions. Most of the analysis of microscopy images taken from neuronal cultures on MEA only consider simple qualitative analysis. Also, the proposed framework aims to standardize the image processing and to compute quantitative useful measures for integrated image-signal studies and further computational simulations. As results show, the implemented microelectrode identification method is robust and so are the implemented neuron segmentation and classification one (with a correct segmentation rate up to 84%). The quantitative information retrieved by the method is highly relevant to assist the integrated signal-image study of recorded electrophysiological signals as well as the physical aspects of the neuron culture on MEA. Although the experiments deal with DRG cell images, cortical and hippocampal cell images could also be processed with small adjustments in the image processing parameter estimation.

Inhibitory effects of devil's claw (secondary root of Harpagophytum procumbens) extract and harpagoside on cytokine production in mouse macrophages.

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Inaba, Kazunori; Murata, Kazuya; Naruto, Shunsuke; Matsuda, Hideaki

2010-04-01

Successive oral administration (50 mg/kg) of a 50% ethanolic extract (HP-ext) of devil's claw, the secondary root of Harpagophytum procumbens, showed a significant anti-inflammatory effect in the rat adjuvant-induced chronic arthritis model. HP-ext dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines [interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] in mouse macrophage cells (RAW 264.7). Harpagoside, a major iridoid glycoside present in devil's claw, was found to be one of the active agents in HP-ext and inhibited the production of IL-1beta, IL-6, and TNF-alpha by RAW 264.7.

The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots

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Kikkawa, Ichiro; Sugimoto, Hideharu; Saita, Kazuo; Ookami, Hitoshi; Nakama, Sueo; Hoshino, Yuichi [Jichi Medical School, Minamikawachi, Tochigi (Japan)

2001-07-01

In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadoliniumdiethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had rediculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further. (author)

The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots

International Nuclear Information System (INIS)

Kikkawa, Ichiro; Sugimoto, Hideharu; Saita, Kazuo; Ookami, Hitoshi; Nakama, Sueo; Hoshino, Yuichi

2001-01-01

In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadoliniumdiethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had rediculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further. (author)

Effects of Vietnamese Sophora root on growth, adhesion, invasion ...

African Journals Online (AJOL)

Background: Vietnamese Sophora Root mainly contains active constituents such as alkaloids, and it has anti-tumour, antibacterial, and anti-inflammatory effects. The objective of the paper was to study the effects of Vietnamese Sophora Root on growth, adhesion, invasion and motility of mouse melanoma B16BL6 cells, and ...

Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications

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Rigosa, J.; Weber, D. J.; Prochazka, A.; Stein, R. B.; Micera, S.

2011-08-01

Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications.

Science.gov (United States)

Rigosa, J; Weber, D J; Prochazka, A; Stein, R B; Micera, S

2011-08-01

Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

Augmentation of glycolytic metabolism by meclizine is indispensable for protection of dorsal root ganglion neurons from hypoxia-induced mitochondrial compromise.

Science.gov (United States)

Zhuo, Ming; Gorgun, Murat F; Englander, Ella W

2016-10-01

To meet energy demands, dorsal root ganglion (DRG) neurons harbor high mitochondrial content, which renders them acutely vulnerable to disruptions of energy homeostasis. While neurons typically rely on mitochondrial energy production and have not been associated with metabolic plasticity, new studies reveal that meclizine, a drug, recently linked to modulations of energy metabolism, protects neurons from insults that disrupt energy homeostasis. We show that meclizine rapidly enhances glycolysis in DRG neurons and that glycolytic metabolism is indispensable for meclizine-exerted protection of DRG neurons from hypoxic stress. We report that supplementation of meclizine during hypoxic exposure prevents ATP depletion, preserves NADPH and glutathione stores, curbs reactive oxygen species (ROS) and attenuates mitochondrial clustering in DRG neurites. Using extracellular flux analyzer, we show that in cultured DRG neurons meclizine mitigates hypoxia-induced loss of mitochondrial respiratory capacity. Respiratory capacity is a measure of mitochondrial fitness and cell ability to meet fluctuating energy demands and therefore, a key determinant of cellular fate. While meclizine is an 'old' drug with long record of clinical use, its ability to modulate energy metabolism has been uncovered only recently. Our findings documenting neuroprotection by meclizine in a setting of hypoxic stress reveal previously unappreciated metabolic plasticity of DRG neurons as well as potential for pharmacological harnessing of the newly discovered metabolic plasticity for protection of peripheral nervous system under mitochondria compromising conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

The functional and anatomical dissection of somatosensory subpopulations using mouse genetics

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Claire E Le Pichon

2014-04-01

Full Text Available The word somatosensation comes from joining the Greek word for body (soma with a word for perception (sensation. Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal root ganglia and at the base of the skull (the trigeminal ganglia. While the neuronal cell bodies are intermingled within the ganglia, the somatosensory system is in reality composed of numerous sub-systems, each specialized to detect distinct stimuli, such as temperature and touch. Historically, somatosensory neurons have been classified using a diverse host of anatomical and physiological parameters, such as the size of the cell body, degree of myelination, histological labeling with markers, specialization of the nerve endings, projection patterns in the spinal cord and brainstem, receptive tuning, and conduction velocity of their action potentials. While useful, the picture that emerged was one of heterogeneity, with many markers at least partially overlapping. More recently, by capitalizing on advances in molecular techniques, researchers have identified specific ion channels and sensory receptors expressed in subsets of sensory neurons. These studies have proved invaluable as they allow genetic access to small subsets of neurons for further molecular dissection. Data being generated from transgenic mice favor the model whereby an array of dedicated neurons is responsible for selectively encoding different modalities. Here we review the current knowledge of the different sensory neuron subtypes in the mouse, the markers used to study them, and the neurogenetic strategies used to define their anatomical projections and functional roles.

Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.

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Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A

2016-03-01

Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested. Copyright © 2015. Published by Elsevier Inc.

Versatility of the ventral approach in bulbar urethroplasty using dorsal, ventral or dorsal plus ventral oral grafts

OpenAIRE

Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; Nunzio, Cosimo De; Giannitsas, Kostas; Shokeir, Ahmed A.

2012-01-01

Objectives To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Patients and methods Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2?cm, range 1.5?5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture...

[Curcumin down-regulates CX3CR1 expression in spinal cord dorsal horn and DRG in neuropathic pain rats].

Science.gov (United States)

Zheng, Jinwei; Zheng, Changjian; Cao, Hong; Li, Jun; Lian, Qingquan

2011-09-01

To investigate the effects of curcumin on the behavior of chronic constrictive injury (CCI) rats and the CX3CR1 expression in spinal cord dorsal horn and dorsal root ganglia (DRG). Seventy-two male SD rats were randomly divided into 4 groups: 1) Sham operation group (Sham); 2) Chronic constrictive injury group (CCI); 3) Curcumin treated group (Cur), administrated with curcumin 100 mg x kg(-1) x d(-1) ip for 14 days after CCI; 4) Solvent contrast group (SC), administrated with an equal volume of solvent for 14 days after CCI. Paw thermal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured on 2 pre-operative and 1, 3, 5, 7, 10, 14 post-operative days respectively. The lumbar segments L4-5 of the spinal cord and the L4, L5 DRG were removed at 3, 7, 14 days after surgery. The expression of CX3CR1 was determined by immunohistochemical staining. Compared with Sham group, PTWL and PMWT in CCI group were significantly lower on each post-operative day (PDRG. In Cur group, PTWL were higher than in CCI group on 7, 10, 14 post-operative day (Pdorsal root ganglia.

Inhibition of calcineurin inhibits the desensitization of capsaicin evoked currents in cultured dorsal root ganglion neurones from adult rats

NARCIS (Netherlands)

Docherty, RJ; Yeats, JC; Bevan, S; Boddeke, HWGM

Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization using electrophysiological methods in cultured dorsal

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

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Lieberman Alexander R

2007-09-01

Full Text Available Abstract Background The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve. Results We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion, most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice. Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses

Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn

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Black Joel A

2012-11-01

Full Text Available Abstract Background Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn. Results Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF, exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals. Conclusions The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach

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Mrinal Pahwa

2013-01-01

Full Text Available Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6–24 months. Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach.

Science.gov (United States)

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D K; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6-24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.

Optimization of micropatterned poly(lactic-co-glycolic acid films for enhancing dorsal root ganglion cell orientation and extension

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Ching-Wen Li

2018-01-01

Full Text Available Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG cells on poly(lactic-co-glycolic acid (PLGA films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation. Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10 μm/10 μm (even, the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 (groove controlled the alignment increases as the ridge size decreases, and when the ratio is larger than 1 (ridge controlled, the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.

PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

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G. R. Hassanzadeh G. Behzadi

2007-08-01

Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

Nogo-receptor gene activity: cellular localization and developmental regulation of mRNA in mice and humans.

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Josephson, Anna; Trifunovski, Alexandra; Widmer, Hans Ruedi; Widenfalk, Johan; Olson, Lars; Spenger, Christian

2002-11-18

Nogo (reticulon-4) is a myelin-associated protein that is expressed in three different splice variants, Nogo-A, Nogo-B, and Nogo-C. Nogo-A inhibits neurite regeneration in the central nervous system. Messenger RNA encoding Nogo is expressed in oligodendrocytes and central and peripheral neurons, but not in astrocytes or Schwann cells. Nogo is a transmembraneous protein; the extracellular domain is termed Nogo-66, and a Nogo-66-receptor (Nogo-R) has been identified. We performed in situ hybridization in human and mouse nervous tissues to map the cellular distribution of Nogo-R gene activity patterns in fetal and adult human spinal cord and sensory ganglia, adult human brain, and the nervous systems of developing and adult mice. In the human fetus Nogo-R was transcribed in the ventral horn of the spinal cord and in dorsal root ganglia. In adult human tissues Nogo-R gene activity was found in neocortex, hippocampus, amygdala, and a subset of large and medium-sized neurons of the dorsal root ganglia. Nogo-R mRNA was not expressed in the adult human spinal cord at detectable levels. In the fetal mouse, Nogo-R was diffusely expressed in brain, brainstem, trigeminal ganglion, spinal cord, and dorsal root ganglia at all stages. In the adult mouse strong Nogo-R mRNA expression was found in neurons in neocortex, hippocampus, amygdala, habenula, thalamic nuclei, brainstem, the granular cell layer of cerebellum, and the mitral cell layer of the olfactory bulb. Neurons in the adult mouse striatum, the medial septal nucleus, and spinal cord did not express Nogo-R mRNA at detectable levels. In summary, Nogo-66-R mRNA expression in humans and mice was observed in neurons of the developing nervous system Expression was downregulated in the adult spinal cord of both species, and specific expression patterns were seen in the adult brain. Copyright 2002 Wiley-Liss, Inc.

Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

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Westlund Karin N

2009-06-01

Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

A biomechanical comparison of four fixed-angle dorsal plates in a finite element model of dorsally-unstable radius fracture.

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Knežević, Josip; Kodvanj, Janoš; Čukelj, Fabijan; Pamuković, Frane; Pavić, Arsen

2017-11-01

To compare the finite element models of two different composite radius fracture patterns, reduced and stabilised with four different fixed-angle dorsal plates during axial, dorsal and volar loading conditions. Eight different plastic models representing four AO/ASIF type 23-A3 distal radius fractures and four AO/ASIF 23-C2 distal radius fractures were obtained and fixed each with 1 of 4 methods: a standard dorsal non-anatomical fixed angle T-plate (3.5mm Dorsal T-plate, Synthes), anatomical fixed-angle double plates (2.4mm LCP Dorsal Distal Radius, Synthes), anatomical fixed angle T-plate (2.4mm Acu-Loc Dorsal Plate, Acumed) or anatomical variable-angle dorsal T-plate (3.5mm, Dorsal Plate, Zrinski). Composite radius with plate and screws were scanned with a 3D optical scanner and later processed in Abaqus Software to generate the finite element model. All models were axially loaded at 3 points (centrally, volarly and dorsally) with 50 N forces to avoid the appearance of plastic deformations of the models. Total displacements at the end of the bone and the stresses in the bones and plates were determined and compared. Maximal von Mises stress in bone for 3-part fracture models was very similar to that in 2-part fracture models. The biggest difference between models and the largest displacements were seen during volar loading. The stresses in all models were the highest above the fracture gap. The best performance in all parameters tested was with the Zrinski plate and the most modest results were with the Synthes T-plate. There was no significant difference between 2-part (AO/ASIF type 23-A3) and 3-part (AO/ASIF 23-C2) fracture models. Maximal stresses in the plates appeared above the fracture gap; therefore, it is worth considering the development of plates without screw holes above the gap. © 2017 Elsevier Ltd. All rights reserved.

Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

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Rosemary C Challis

Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

Dync1h1 Mutation Causes Proprioceptive Sensory Neuron Loss and Impaired Retrograde Axonal Transport of Dorsal Root Ganglion Neurons.

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Zhao, Jing; Wang, Yi; Xu, Huan; Fu, Yuan; Qian, Ting; Bo, Deng; Lu, Yan-Xin; Xiong, Yi; Wan, Jun; Zhang, Xiang; Dong, Qiang; Chen, Xiang-Jun

2016-07-01

Sprawling (Swl) is a radiation-induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1). This study is to investigate the phenotype and the underlying mechanism of the Dync1h1 mutant. To display the phenotype of Swl mutant mice, we examined the embryos of homozygous (Swl/Swl) and heterozygous (Swl/+) mice and their postnatal dorsal root ganglion (DRG) of surviving Swl/+ mice. The Swl/+ mice could survive for a normal life span, while Swl/Swl could only survive till embryonic (E) 8.5 days. Excessive apoptosis of Swl/+ DRG neurons was revealed during E11.5-E15.5 days, and the peak rate was at E13.5 days. In vitro study of mutated DRG neurons showed impaired retrograde transport of dynein-driven nerve growth factor (NGF). Mitochondria, another dynein-driven cargo, demonstrated much slower retrograde transport velocity in Swl/+ neurons than in wild-type (WT) neurons. Nevertheless, the Swl, Loa, and Cra mutations did not affect homodimerization of DYNC1H1. The Swl/Swl mutation of Dync1h1 gene led to embryonic mal-development and lethality, whereas the Swl/+ DRG neurons demonstrated deficient retrograde transport in dynein-driven cargos and excessive apoptosis during mid- to late-developmental stages. The underlying mechanism of the mutation may not be due to impaired homodimerization of DYNC1H1. © 2016 John Wiley & Sons Ltd.

The subacute damage of the dorsal root ganglion induced by collagenase in rats: a study on the ultrastructure of neurons

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Li Heping; Zhuang Wenquan; Yang Jianyong; Chen Wei

2005-01-01

Objective: To study the effects of collagenase on the ultrastructure of dorsal root ganglion (DRG) in rats. The safety of collagenase on nerve tissue was investigated. Additionally, the safety of percutaneous collagenase chemonucleolysis (PCCN) on nerve tissue was evaluated. Methods: In total 27 male, healthy SD rats were enrolled. All rats were randomized into 3 groups: normal group (9 rats), subacute damage of collagenase group (9 rats), subacute intervention-analogue group (9 rats). The left L5 DRG was exposed in each rat. One milliliter of the collagenase solution (300 units) was carefully applied to the exposed DRG in collagenase group, and one milliliter of the isotonic saline was applied to the exposed DRG in intervention-analogue group. The morphology of the DRG under electron microscope were analyzed 7-9 days after the procedures. Results: The types, number, and morphology of cells; the membrane of neutrons; the nerve fibers and blood vessels in DRG had not been changed in all groups observed under optic microscope. The difference of the ultrastructure of neutrons in DRG among the normal groups, intervention-analogue group and collagenase group was significant: 1) The eccentric nucleolus were revealed; 2) Swelling mitochondria and absence of mitochondria crests and vesicles. Cytoclasis and apoptosis of neutrons had not been observed under electron microscope. Conclusion: The collagenase used in PCCN dose have a certain damage to the neutreons in DRG. In the procedure of PCCN, the volume and dosage of collagenase should be carefully selected and the intervention should be precisely performed by experienced hands. (authors)

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

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Schill, Ellen Merrick; Lake, Jonathan I.; Tusheva, Olga A.; Nagy, Nandor; Bery, Saya K.; Foster, Lynne; Avetisyan, Marina; Johnson, Stephen L.; Stenson, William F.; Goldstein, Allan M.; Heuckeroth, Robert O.

2016-01-01

Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. PMID:26586201

p38 mediates mechanical allodynia in a mouse model of type 2 diabetes

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Hong Yu

2010-05-01

Full Text Available Abstract Background Painful Diabetic Neuropathy (PDN affects more than 25% of patients with type 2 diabetes; however, the pathogenesis remains unclear due to lack of knowledge of the molecular mechanisms leading to PDN. In our current study, we use an animal model of type 2 diabetes in order to understand the roles of p38 in PDN. Previously, we have demonstrated that the C57BLK db/db (db/db mouse, a model of type 2 diabetes that carries the loss-of-function leptin receptor mutant, develops mechanical allodynia in the hind paws during the early stage (6-12 wk of age of diabetes. Using this timeline of PDN, we can investigate the signaling mechanisms underlying mechanical allodynia in the db/db mouse. Results We studied the role of p38 in lumbar dorsal root ganglia (LDRG during the development of mechanical allodynia in db/db mice. p38 phosphorylation was detected by immunoblots at the early stage of mechanical allodynia in LDRG of diabetic mice. Phosphorylated p38 (pp38 immunoreactivity was detected mostly in the small- to medium-sized LDRG neurons during the time period of mechanical allodynia. Treatment with an antibody against nerve growth factor (NGF significantly inhibited p38 phosphorylation in LDRG of diabetic mice. In addition, we detected higher levels of inflammatory mediators, including cyclooxygenase (COX 2, inducible nitric oxide synthases (iNOS, and tumor necrosis factor (TNF-α in LDRG neurons of db/db mice compared to non-diabetic db+ mice. Intrathecal delivery of SB203580, a p38 inhibitor, significantly inhibited the development of mechanical allodynia and the upregulation of COX2, iNOS and TNF-α. Conclusions Our findings suggest that NGF activated-p38 phosphorylation mediates mechanical allodynia in the db/db mouse by upregulation of multiple inflammatory mediators in LDRG.

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy.

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Lakritz, Jessica R; Yalamanchili, Samshita; Polydefkis, Michael J; Miller, Andrew D; McGrath, Michael S; Williams, Kenneth C; Burdo, Tricia H

2017-08-01

Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

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Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

Personal authentication through dorsal hand vein patterns

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Hsu, Chih-Bin; Hao, Shu-Sheng; Lee, Jen-Chun

2011-08-01

Biometric identification is an emerging technology that can solve security problems in our networked society. A reliable and robust personal verification approach using dorsal hand vein patterns is proposed in this paper. The characteristic of the approach needs less computational and memory requirements and has a higher recognition accuracy. In our work, the near-infrared charge-coupled device (CCD) camera is adopted as an input device for capturing dorsal hand vein images, it has the advantages of the low-cost and noncontact imaging. In the proposed approach, two finger-peaks are automatically selected as the datum points to define the region of interest (ROI) in the dorsal hand vein images. The modified two-directional two-dimensional principal component analysis, which performs an alternate two-dimensional PCA (2DPCA) in the column direction of images in the 2DPCA subspace, is proposed to exploit the correlation of vein features inside the ROI between images. The major advantage of the proposed method is that it requires fewer coefficients for efficient dorsal hand vein image representation and recognition. The experimental results on our large dorsal hand vein database show that the presented schema achieves promising performance (false reject rate: 0.97% and false acceptance rate: 0.05%) and is feasible for dorsal hand vein recognition.

Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

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Jason A Bleedorn

Full Text Available Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK, phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt, and mammalian target of rapamycin (mTOR. However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK's, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α, brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, c-jun, and c-fos in dorsal root ganglion (DRG of the brachial intumescence were performed. There was a significant increase in signaling through MAPK's including extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05. However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the

Neuroradiological evaluation of dorsal cyst malformations

International Nuclear Information System (INIS)

Utsunomiya, Hidetsuna; Hayashi, Takashi; Hashimoto, Takeo; Matsuishi, Toyojiro; Okudera, Toshio.

1988-01-01

We discussed six cases with dorsal cyst malformations listing their neuroradiological observations and proposed to differentiate between the holosphere and hemisphere as defined by Yokota (1984). The cases were divided into holospheric and hemispheric groups depending on the continuity of their frontal lobe midlines. Cases 1, 2 and 3 were placed in the holospheric group because of their unseparated frontal lobe sbeneath the partially formed anterior interhemispheric fissures. Cases 4, 5 and 6 were grouped in the hemisphere due to the completion of the interhemispheric fissures. There has been a tendency in recent years for most cases of cerebral malformations having an endogenous dorsal cyst with monoventricular configuration to be diagnosed as holoprosencephaly. However, we believe that only patients who have a dorsal cyst in the holospheric brain should be included, and the others in the hemispheric brain, which is capable of completing hemispheric cleavage, should not. Therefore, we emphasize the importance of correctly identifying the holospheric state in the dorsal cyst malformations for diagnosing holoprosencephaly. (author)

Neural-Dural Transition at the Thoracic and Lumbar Spinal Nerve Roots: A Histological Study of Human Late-Stage Fetuses

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Kwang Ho Cho

2016-01-01

Full Text Available Epidural blocks have been used extensively in infants. However, little histological information is available on the immature neural-dural transition. The neural-dural transition was histologically investigated in 12 late-stage (28–30 weeks fetuses. The dural sheath of the spinal cord was observed to always continue along the nerve roots with varying thicknesses between specimens and segments, while the dorsal root ganglion sheath was usually very thin or unclear. Immature neural-dural transitions were associated with effective anesthesia. The posterior radicular artery was near the dorsal root ganglion and/or embedded in the nerve root, whereas the anterior radicular artery was separated from the nearest nerve root. The anterior radicular artery was not associated with the dural sheath but with thin mesenchymal tissue. The numbers of radicular arteries tended to become smaller in larger specimens. Likewise, larger specimens of the upper thoracic and lower lumbar segments did not show the artery. Therefore, elimination of the radicular arteries to form a single artery of Adamkiewicz was occurring in late-stage fetuses. The epidural space was filled with veins, and the loose tissue space extended ventrolaterally to the subpleural tissue between the ribs. Consequently, epidural blocks in infants require special attention although immature neural-dural transitions seemed to increase the effect.

Subplate in the developing cortex of mouse and human

DEFF Research Database (Denmark)

Wang, Wei Zhi; Hoerder-Suabedissen, Anna; Oeschger, Franziska M

2010-01-01

Abstract The subplate is a largely transient zone containing precocious neurons involved in several key steps of cortical development. The majority of subplate neurons form a compact layer in mouse, but are dispersed throughout a much larger zone in the human. In rodent, subplate neurons are among...... several genes that are specifically expressed in the subplate layer of the rodent dorsal cortex. Here we examined the human subplate for some of these markers. In the human dorsal cortex, connective tissue growth factor-positive neurons can be seen in the ventricular zone at 15-22 postconceptional weeks...... growth factor- and nuclear receptor-related 1-positive cells are two distinct cell populations of the human subplate. Furthermore, our microarray analysis in rodent suggested that subplate neurons produce plasma proteins. Here we demonstrate that the human subplate also expresses alpha2zinc...

Organ dose conversion coefficients based on a voxel mouse model and MCNP code for external photon irradiation.

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Zhang, Xiaomin; Xie, Xiangdong; Cheng, Jie; Ning, Jing; Yuan, Yong; Pan, Jie; Yang, Guoshan

2012-01-01

A set of conversion coefficients from kerma free-in-air to the organ absorbed dose for external photon beams from 10 keV to 10 MeV are presented based on a newly developed voxel mouse model, for the purpose of radiation effect evaluation. The voxel mouse model was developed from colour images of successive cryosections of a normal nude male mouse, in which 14 organs or tissues were segmented manually and filled with different colours, while each colour was tagged by a specific ID number for implementation of mouse model in Monte Carlo N-particle code (MCNP). Monte Carlo simulation with MCNP was carried out to obtain organ dose conversion coefficients for 22 external monoenergetic photon beams between 10 keV and 10 MeV under five different irradiation geometries conditions (left lateral, right lateral, dorsal-ventral, ventral-dorsal, and isotropic). Organ dose conversion coefficients were presented in tables and compared with the published data based on a rat model to investigate the effect of body size and weight on the organ dose. The calculated and comparison results show that the organ dose conversion coefficients varying the photon energy exhibits similar trend for most organs except for the bone and skin, and the organ dose is sensitive to body size and weight at a photon energy approximately <0.1 MeV.

Sunscreen Use on the Dorsal Hands at the Beach

International Nuclear Information System (INIS)

Warren, D. B.; Hobbs, J. B.; Jr, R. F. W.; Riahi, R. R.

2013-01-01

Since skin of the dorsal hands is a known site for the development of cutaneous squamous cell carcinoma, an epidemiologic investigation was needed to determine if beachgoers apply sunscreen to the dorsal aspect of their hands as frequently as they apply it to other skin sites. Aim. The aim of the current study was to compare the use of sunscreen on the dorsal hands to other areas of the body during subtropical late spring and summer sunlight exposure at the beach. Materials and Methods. A cross-sectional survey from a convenience sample of beachgoers was designed to evaluate responded understanding and protective measures concerning skin cancer on the dorsal hands in an environment with high natural UVR exposure. Results. A total of 214 surveys were completed and analyzed. Less than half of subjects (105, 49%) applied sunscreen to their dorsal hands. Women applied sunscreen to the dorsal hands more than men (55% women versus 40% men, ρ=0.04 ). Higher Fitzpatrick Skin Type respondents were less likely to protect their dorsal hands from ultraviolet radiation (ρ=0.001 ). Conclusions. More public education focused on dorsal hand protection from ultraviolet radiation damage is necessary to reduce the risk for squamous cell carcinomas of the hands.

Nanoparticle-Encapsulated Curcumin Inhibits Diabetic Neuropathic Pain Involving the P2Y12 Receptor in the Dorsal Root Ganglia

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Tianyu Jia

2018-01-01

Full Text Available Diabetic peripheral neuropathy results in diabetic neuropathic pain (DNP. Satellite glial cells (SGCs enwrap the neuronal soma in the dorsal root ganglia (DRG. The purinergic 2 (P2 Y12 receptor is expressed on SGCs in the DRG. SGC activation plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Because curcumin has poor metabolic stability in vivo and low bioavailability, nanoparticle-encapsulated curcumin was used to improve its targeting and bioavailability. In the present study, our aim was to investigate the effects of nanoparticle-encapsulated curcumin on DNP mediated by the P2Y12 receptor on SGCs in the rat DRG. Diabetic peripheral neuropathy increased the expression levels of the P2Y12 receptor on SGCs in the DRG and enhanced mechanical and thermal hyperalgesia in rats with diabetes mellitus (DM. Up-regulation of the P2Y12 receptor in SGCs in the DRG increased the production of pro-inflammatory cytokines. Up-regulation of interleukin-1β (IL-1β and connexin43 (Cx43 resulted in mechanical and thermal hyperalgesia in rats with DM. The nanoparticle-encapsulated curcumin decreased up-regulated IL-1β and Cx43 expression and reduced levels of phosphorylated-Akt (p-Akt in the DRG of rats with DM. The up-regulation of P2Y12 on SGCs and the up-regulation of the IL-1β and Cx43 in the DRG indicated the activation of SGCs in the DRG. The nano-curcumin treatment inhibited the activation of SGCs accompanied by its anti-inflammatory effect to decrease the up-regulated CGRP expression in the DRG neurons. Therefore, the nanoparticle-encapsulated curcumin treatment decreased the up-regulation of the P2Y12 receptor on SGCs in the DRG and decreased mechanical and thermal hyperalgesia in rats with DM.

GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

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Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

2016-03-01

Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat.

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Thibault, Karine; Rivals, Isabelle; M'Dahoma, Saïd; Dubacq, Sophie; Pezet, Sophie; Calvino, Bernard

2013-11-01

Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Yan Chen

2016-01-01

Full Text Available Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2 on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

2016-01-01

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

Agenesis of the dorsal pancreas

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Schnedl, Wolfgang J; Piswanger-Soelkner, Claudia; Wallner, Sandra J; Krause, Robert; Lipp, Rainer W

2009-01-01

During the last 100 years in medical literature, there are only 54 reports, including the report of Pasaoglu et al (World J Gastroenterol 2008; 14: 2915-2916), with clinical descriptions of agenesis of the dorsal pancreas in humans. Agenesis of the dorsal pancreas, a rare congenital pancreatic malformation, is associated with some other medical conditions such as hyperglycemia, abdominal pain, pancreatitis and a few other diseases. In approximately 50% of reported patients with this congenital malformation, hyperglycemia was demonstrated. Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose, oral glucose tolerance test, glycated hemoglobin and medical treatment would be a future goal. Since autosomal dominant transmission has been suggested in single families, more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease. With this letter to the editor, we aim to increase available information for the better understanding of this rare disease. PMID:19140241

Emergent properties during dorsal closure in Drosophila morphogenesis

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Peralta, X G; Toyama, Y; Edwards, G S; Kiehart, D P

2008-01-01

Dorsal closure is an essential stage of Drosophila development that is a model system for research in morphogenesis and biological physics. Dorsal closure involves an orchestrated interplay between gene expression and cell activities that produce shape changes, exert forces and mediate tissue dynamics. We investigate the dynamics of dorsal closure based on confocal microscopic measurements of cell shortening in living embryos. During the mid-stages of dorsal closure we find that there are fluctuations in the width of the leading edge cells but the time-averaged analysis of measurements indicate that there is essentially no net shortening of cells in the bulk of the leading edge, that contraction predominantly occurs at the canthi as part of the process for zipping together the two leading edges of epidermis and that the rate constant for zipping correlates with the rate of movement of the leading edges. We characterize emergent properties that regulate dorsal closure, i.e., a velocity governor and the coordination and synchronization of tissue dynamics

Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

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Dougherty Patrick M

2009-07-01

Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation

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Zhang AL

2017-02-01

Full Text Available Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China Abstract: Lumbar disc herniation (LDH is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP was implanted in the left L5 dorsal root ganglion (DRG to mimic LDH in rats. We investigated the expression of NF-κB and the components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting and immunofluorescence for the related molecules, including NLRP3, apoptosis-associated speck-like protein containing caspase-1 activator domain (ASC, caspase-1, interleukin (IL-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and calcitonin gene-related peptide (CGRP were examined. In the NP-treated group, the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was able to inhibit expression and activation of the molecules (NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 and relieve the pain in rats. Our study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation. Keywords: pain, NLRP3, NF-κB, dorsal root ganglion, nucleus pulposus

Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

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Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

2016-07-01

Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

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Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

2017-03-15

A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

Low Frequency Electroacupuncture Alleviated Spinal Nerve Ligation Induced Mechanical Allodynia by Inhibiting TRPV1 Upregulation in Ipsilateral Undamaged Dorsal Root Ganglia in Rats

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Yong-Liang Jiang

2013-01-01

Full Text Available Neuropathic pain is an intractable problem in clinical practice. Accumulating evidence shows that electroacupuncture (EA with low frequency can effectively relieve neuropathic pain. Transient receptor potential vanilloid type 1 (TRPV1 plays a key role in neuropathic pain. The study aimed to investigate whether neuropathic pain relieved by EA administration correlates with TRPV1 inhibition. Neuropathic pain was induced by right L5 spinal nerve ligation (SNL in rats. 2 Hz EA stimulation was administered. SNL induced mechanical allodynia in ipsilateral hind paw. SNL caused a significant reduction of TRPV1 expression in ipsilateral L5 dorsal root ganglia (DRG, but a significant up-regulation in ipsilateral L4 and L6 DRGs. Calcitonin gene-related peptide (CGRP change was consistent with that of TRPV1. EA alleviated mechanical allodynia, and inhibited TRPV1 and CGRP overexpressions in ipsilateral L4 and L6 DRGs. SNL did not decrease pain threshold of contralateral hind paw, and TRPV1 expression was not changed in contralateral L5 DRG. 0.001, 0.01 mg/kg TRPV1 agonist 6′-IRTX fully blocked EA analgesia in ipsilateral hind paw. 0.01 mg/kg 6′-IRTX also significantly decreased pain threshold of contralateral paw. These results indicated that inhibition of TRPV1 up-regulation in ipsilateral adjacent undamaged DRGs contributed to low frequency EA analgesia for mechanical allodynia induced by spinal nerve ligation.

Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol.

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Naziroğlu, Mustafa; Ozgül, Cemil

2012-02-01

Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca(2+) gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.

Characterization of a chondroitin sulfate hydrogel for nerve root regeneration

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Conovaloff, Aaron; Panitch, Alyssa

2011-10-01

Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains.

Wrist Hypothermia Related to Continuous Work with a Computer Mouse: A Digital Infrared Imaging Pilot Study

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Jelena Reste

2015-08-01

Full Text Available Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad. The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C, while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia.

Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

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Schuhmacher, Laura-Nadine; Smith, Ewan St John

2016-12-13

Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

Age- and sex-dependence of dopamine release and capacity for recovery identified in the dorsal striatum of C57/Bl6J mice.

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Emma Arvidsson

Full Text Available The dorsal striatum is the main input structure of the basal ganglia and the major target area of dopaminergic projections originating in the substantia nigra pars compacta. Heavily involved in the regulation of voluntary movement and habit formation, this structure is of strong importance in Parkinson's disease, obsessive-compulsive disorder, Tourette's syndrome and addiction. The C57/Bl6J mouse strain, the most commonly used strain in preclinical research today, is frequently used as a model organism for analysis of dopaminergic parameters implicated in human pathophysiology. Several components of the dopamine system have been shown to vary with age and sex, however knowledge of the contribution of these factors for dopamine release kinetics in the C57/Bl6J mouse strain is lacking. In the present study, we used an intracranial KCl-stimulation challenge paradigm to provoke release from dopaminergic terminals in the dorsal striatum of anaesthetized C57/Bl6J mice. By high-speed in vivo chronoamperometric recordings, we analyzed DA release parameters in male and female mice of two different ages. Our experiments demonstrate elevated DA amplitudes in adult compared to young mice of both sexes and higher DA amplitudes in females compared to males at both ages. Adult mice exhibited higher recovery capabilities after repeated stimulation than did young mice and also showed a lower variability in the kinetic parameters trise and t80 between stimulations. These results identified age- and sex- dimorphisms in DA release parameters and point to the importance of taking these dimorphisms into account when utilizing the C57/Bl6J mouse strain as model for neurological and neuropsychiatric disorders.

A new class of ubiquitin extension proteins secreted by the dorsal pharyngeal gland in plant parasitic cyst nematodes.

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Tytgat, Tom; Vanholme, Bartel; De Meutter, Jan; Claeys, Myriam; Couvreur, Marjolein; Vanhoutte, Isabelle; Gheysen, Greetje; Van Criekinge, Wim; Borgonie, Gaetan; Coomans, August; Gheysen, Godelieve

2004-08-01

By performing cDNA AFLP on pre- and early parasitic juveniles, we identified genes encoding a novel type of ubiquitin extension proteins secreted by the dorsal pharyngeal gland in the cyst nematode Heterodera schachtii. The proteins consist of three domains, a signal peptide for secretion, a mono-ubiquitin domain, and a short C-terminal positively charged domain. A gfp-fusion of this protein is targeted to the nucleolus in tobacco BY-2 cells. We hypothesize that the C-terminal peptide might have a regulatory function during syncytium formation in plant roots.

Metabotropic glutamate receptor-5 and protein kinase C-epsilon increase in dorsal root ganglion neurons and spinal glial activation in an adolescent rat model of painful neck injury.

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Weisshaar, Christine L; Dong, Ling; Bowman, Alex S; Perez, Federico M; Guarino, Benjamin B; Sweitzer, Sarah M; Winkelstein, Beth A

2010-12-01

There is growing evidence that neck pain is common in adolescence and is a risk factor for the development of chronic neck pain in adulthood. The cervical facet joint and its capsular ligament is a common source of pain in the neck in adults, but its role in adolescent pain remains unknown. The aim of this study was to define the biomechanics, behavioral sensitivity, and indicators of neuronal and glial activation in an adolescent model of mechanical facet joint injury. A bilateral C6-C7 facet joint distraction was imposed in an adolescent rat and biomechanical metrics were measured during injury. Following injury, forepaw mechanical hyperalgesia was measured, and protein kinase C-epsilon (PKCɛ) and metabotropic glutamate receptor-5 (mGluR5) expression in the dorsal root ganglion and markers of spinal glial activation were assessed. Joint distraction induced significant mechanical hyperalgesia during the 7 days post-injury (p capsule during injury were 32.8 ± 12.9%, which were consistent with the strains associated with comparable degrees of hypersensitivity in the adult rat. These results suggest that adolescents may have a lower tissue tolerance to induce pain and associated nociceptive response than do adults.

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

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Sandeep Gupta

2018-02-01

Full Text Available Summary: Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC- or induced pluripotent stem cell (hiPSC-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs, which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. : In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol. Keywords: spinal cord, neurons, sensory interneurons, proprioception, mechanosensation, human embryonic stem cells, induced pluripotent stem cells, directed differentiation, primate spinal cord, mouse spinal cord

Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy

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Egensperger Rupert

2009-07-01

Full Text Available Abstract Background Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG cells leading to sensory polyneuropathy (PNP. We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden. Results A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s ± 1,68 m/s; cisplatin + rhEPO 49,66 m/s ± 1,26 m/s; control 55,01 m/s ± 1,88 m/s; p Conclusion The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.

Description of Meloidogyne minor n.sp. (Nematoda: Meloidogynidae), a root-knot nematode associated with yellow patch disease in golf courses

NARCIS (Netherlands)

Karssen, G.; Bolk, R.J.; Aelst, van A.C.; Beld, van den I.; Kox, L.F.F.; Korthals, G.W.; Molendijk, L.P.G.; Zijlstra, C.; Hoof, van R.A.; Cook, R.

2004-01-01

A relatively small root-knot nematode, Meloidogyne minor n. sp., is described and illustrated from tomato from the Netherlands. This new species is characterised by the following features: female with dorsally curved stylet, 14 Pm long, with transversely ovoid knobs slightly sloping backwards from

Differential effects of temperature on acid-activated currents mediated by TRPV1 and ASIC channels in rat dorsal root ganglion neurons.

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Neelands, Torben R; Zhang, Xu-Feng; McDonald, Heath; Puttfarcken, Pamela

2010-05-06

Elevated temperature and decreased extracellular pH are hallmarks of inflammatory pain states. Dorsal root ganglia (DRG) neurons are integral in transferring painful stimuli from the periphery to central sites. This study investigated the effect of elevated temperatures on the response of DRG neurons to acute application of acidic solutions. At room temperature (22 degrees C), in response to pH 5.5, there were a variety of kinetic responses consistent with differential expression of TRPV1 and ASIC channels. Increasing the temperature resulted in a significant increase in the peak and total current mediated by TRPV1 in response to an acidic solution. In contrast, the amplitude of a fast activating, rapidly inactivating ASIC1-like current was not affected by increasing the temperature but did result in an increased rate of desensitization that reduced the total current level. This effect on the rate of desensitization was temperature-dependent and could be reversed by returning to 22 degrees C. Likewise, cells exhibiting slowly inactivating ASIC2-like responses also had temperature-dependent increase in the rate of desensitization. The ASIC2-like responses and the TRPV1 responses tended to decrease in amplitude with repetitive application of pH 5.5 even at 22 degrees C. The rate of desensitization of ASIC-like currents activated by less acidic solutions (pH 6.8) was also increased in a temperature-dependent manner. Finally, acidic pH reduced threshold to trigger action potentials, however, the pattern of action potential firing was shaped by the distribution of ASIC and TRPV1 channels. These results indicate that the ambient temperature at which acidosis occurs has a profound effect on the contribution of ASIC and TRPV1 channels, therefore, altering the neuronal excitability. Copyright 2010 Elsevier B.V. All rights reserved.

HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection.

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Sharthiya, Harsh; Seng, Chanmoly; Van Kuppevelt, T H; Tiwari, Vaibhav; Fornaro, Michele

2017-06-01

The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry. Finally, a cytokine array profile generated during HSV-1 infection in DRG explant indicated an enhanced expression of chemokines (LIX, TIMP-2, and M-CSF)-known regulators of HS. Taken together, these results highlight the significance of HS during HSV-1 entry in DRG explant. Further investigation is needed to understand which isoforms of 3-O-sulfotransferase (3-OST)-generated HS contributed during HSV-1 infection and associated cell damage.

Dorsal finger texture recognition: Investigating fixed-length SURF

DEFF Research Database (Denmark)

Hartung, Daniel; Kückelhahn, Jesper

2012-01-01

We seek to create fixed-length features from dorsal finger skin images extracted by the SURF interest point detector to combine it in the privacy enhancing helper data scheme. The source of the biometric samples is the GUC45 database which features finger vein, fingerprint and dorsal finger skin...

Meloidogyne luci n. sp. (Nematoda: Meloidogynidae), a root-knot nematode parasitising different crops in Brazil, Chile and Iran

NARCIS (Netherlands)

Carneiro, R.M.D.G.; Correa, V.R.; Almeida, M.R.A.; Gomes, A.C.M.M.; Deimi, A.M.; Castagnone-Sereno, P.; Karssen, G.

2014-01-01

A new root-knot nematode parasitising vegetables, flowers and fruits in Brazil, Iran and Chile, is described as Meloidogyne luci n. sp. The female has an oval to squarish perineal pattern with a low to moderately high dorsal arc and without shoulders, similar to M. ethiopica. The female stylet is

Neurotoxicity of cytarabine (Ara-C) in dorsal root ganglion neurons originates from impediment of mtDNA synthesis and compromise of mitochondrial function.

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Zhuo, Ming; Gorgun, Murat F; Englander, Ella W

2018-06-01

Peripheral Nervous System (PNS) neurotoxicity caused by cancer drugs hinders attainment of chemotherapy goals. Due to leakiness of the blood nerve barrier, circulating chemotherapeutic drugs reach PNS neurons and adversely affect their function. Chemotherapeutic drugs are designed to target dividing cancer cells and mechanisms underlying their toxicity in postmitotic neurons remain to be fully clarified. The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons. For proof of mechanism study, we chose cytarabine (ara-C), an antimetabolite used in treatment of hematological cancers. Ara-C is a cytosine analog that terminates DNA synthesis. To investigate how ara-C affects postmitotic neurons, which replicate mitochondrial but not genomic DNA, we adapted a model of Dorsal Root Ganglion (DRG) neurons. We showed that DNA polymerase γ, which is responsible for mtDNA synthesis, is inhibited by ara-C and that sublethal ara-C exposure of DRG neurons leads to reduction in mtDNA content, ROS generation, oxidative mtDNA damage formation, compromised mitochondrial respiration and diminution of NADPH and GSH stores, as well as, activation of the DNA damage response. Hence, it is plausible that in ara-C exposed DRG neurons, ROS amplified by the high mitochondrial content shifts from physiologic to pathologic levels signaling stress to the nucleus. Combined, the findings suggest that ara-C neurotoxicity in DRG neurons originates in mitochondria and that continuous mtDNA synthesis and reliance on oxidative phosphorylation for energy needs sensitize the highly metabolic neurons to injury by mtDNA synthesis terminating cancer drugs. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression and distribution patterns of Mas-related gene receptor subtypes A-H in the mouse intestine: inflammation-induced changes.

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Avula, Leela Rani; Buckinx, Roeland; Favoreel, Herman; Cox, Eric; Adriaensen, Dirk; Van Nassauw, Luc; Timmermans, Jean-Pierre

2013-05-01

Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and

Functional connectivity of the dorsal striatum in female musicians

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Shoji eTanaka

2016-04-01

Full Text Available The dorsal striatum (caudate/putamen is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians.Resting state functional magnetic resonance imaging (fMRI data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to graph theoretical analysis and functional connectivity analysis. The graph theoretical analysis of the entire brain revealed that the degree, which represents the number of connections, of the bilateral putamen was significantly lower in musicians than in nonmusicians. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum and between the left caudate nucleus and cerebellum. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum, with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers. To the best of our knowledge, this is the first study suggesting that long-term musical training results in a less extensive or selective functional network of the dorsal striatum.

Insulin-like growth factor-1 prevents dorsal root ganglion neuronal tyrosine kinase receptor expression alterations induced by dideoxycytidine in vitro.

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Liu, Huaxiang; Lu, Jing; He, Yong; Yuan, Bin; Li, Yizhao; Li, Xingfu

2014-03-01

Dideoxycytidine (zalcitabine, ddC) produces neurotoxic effects. It is particularly important to understand the toxic effects of ddC on different subpopulations of dorsal root ganglion (DRG) neurons which express distinct tyrosine kinase receptor (Trk) and to find therapeutic factors for prevention and therapy for ddC-induced peripheral sensory neuropathy. Insulin-like growth factor-1 (IGF-1) has been shown to have neurotrophic effects on DRG sensory neurons. However, little is known about the effects of ddC on distinct Trk (TrkA, TrkB, and TrkC) expression in DRG neurons and the neuroprotective effects of IGF-1 on ddC-induced neurotoxicity. Here, we have tested the extent to which the expression of TrkA, TrkB, and TrkC receptors in primary cultured DRG neurons is affected by ddC in the presence or absence of IGF-1. In this experiment, we found that exposure of 5, 25, and 50 μmol/L ddC caused a dose-dependent decrease of the mRNA, protein, and the proportion of TrkA-, TrkB-, and TrkC-expressing neurons. IGF-1 (20 nmol/L) could partially reverse the decrease of TrkA and TrkB, but not TrkC, expression with ddC exposure. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) blocked the effects of IGF-1. These results suggested that the subpopulations of DRG neurons which express distinct TrkA, TrkB, and TrkC receptors were affected by ddC exposure. IGF-1 might relieve the ddC-induced toxicity of TrkA- and TrkB-, but not TrkC-expressing DRG neurons. These data offer new clues for a better understanding of the association of ddC with distinct Trk receptor expression and provide new evidence of the potential therapeutic role of IGF-1 on ddC-induced neurotoxicity.

Serotonergic versus Nonserotonergic Dorsal Raphe Projection Neurons: Differential Participation in Reward Circuitry

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Ross A. McDevitt

2014-09-01

Full Text Available The dorsal raphe nucleus (DRN contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes. To explore DRN heterogeneity, we used a simultaneous two-vector knockout/optogenetic stimulation strategy, as well as cre-induced and cre-silenced vectors in several cre-expressing transgenic mouse lines. We found that the DRN is capable of reinforcing behavior primarily via nonserotonergic neurons, for which the main projection target is the ventral tegmental area (VTA. Furthermore, these nonserotonergic projections provide glutamatergic excitation of VTA dopamine neurons and account for a large majority of the DRN-VTA pathway. These findings help to resolve apparent discrepancies between the roles of serotonin versus the DRN in behavioral reinforcement.

Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.

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Pawela, Christopher P; Kramer, Jeffery M; Hogan, Quinn H

2017-02-15

Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

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Berta Temugin

2012-03-01

Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats.

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Yang, Dan; Liang, Xiao-Chun; Shi, Yue; Sun, Qing; Liu, Di; Liu, Wei; Zhang, Hong

2016-01-01

To examine the mechanism underlying the beneficial role of cinnamaldehyde on oxidative damage and apoptosis in high glucose (HG)-induced dorsal root ganglion (DRG) neurons in vitro. HG-treated DRG neurons were developed as an in vitro model of diabetic neuropathy. The neurons were randomly divided into five groups: the control group, the HG group and the HG groups treated with 25, 50 and 100 nmol/L cinnamaldehyde, respectively. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis rate was evaluated by the in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. The intracellular level of reactive oxygen species (ROS) was measured with flow cytometry. Expression of nuclear factor-kappa B (NF-κB), inhibitor of κB (IκB), phosphorylated IκB (p-IκB), tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and caspase-3 were determined by western blotting and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were also measured by western blotting. Cinnamaldehyde reduced HG-induced loss of viability, apoptosis and intracellular generation of ROS in the DRG neurons via inhibiting NF-κB activity. The western blot assay results showed that the HG-induced elevated expressions of NF-κB, IκB and p-IκB were remarkably reduced by cinnamaldehyde treatment in a dose-dependent manner (P neurons, but also lowered the elevated IL-6, TNF-α, cyclo-oxygenase and inducible nitric oxide synthase levels, indicating a reduction in inflammatory damage. Cinnamaldehyde protected DRG neurons from the deleterious effects of HG through inactivation of NF-κB pathway but not through activation of Nrf2/HO-1. And thus cinnamaldehyde may have potential application as a treatment for DPN.

Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons.

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Fukuoka, Tetsuo; Kobayashi, Kimiko; Yamanaka, Hiroki; Obata, Koichi; Dai, Yi; Noguchi, Koichi

2008-09-10

We compared the distribution of the alpha-subunit mRNAs of voltage-gated sodium channels Nav1.1-1.3 and Nav1.6-1.9 and a related channel, Nax, in histochemically identified neuronal subpopulations of the rat dorsal root ganglia (DRG). In the naïve DRG, the expression of Nav1.1 and Nav1.6 was restricted to A-fiber neurons, and they were preferentially expressed by TrkC neurons, suggesting that proprioceptive neurons possess these channels. Nav1.7, -1.8, and -1.9 mRNAs were more abundant in C-fiber neurons compared with A-fiber ones. Nax was evenly expressed in both populations. Although Nav1.8 and -1.9 were preferentially expressed by TrkA neurons, other alpha-subunits were expressed independently of TrkA expression. Actually, all IB4(+) neurons expressed both Nav1.8 and -1.9, and relatively limited subpopulations of IB4(+) neurons (3% and 12%, respectively) expressed Nav1.1 and/or Nav1.6. These findings provide useful information in interpreting the electrophysiological characteristics of some neuronal subpopulations of naïve DRG. After L5 spinal nerve ligation, Nav1.3 mRNA was up-regulated mainly in A-fiber neurons in the ipsilateral L5 DRG. Although previous studies demonstrated that nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) reversed this up-regulation, the Nav1.3 induction was independent of either TrkA or GFRalpha1 expression, suggesting that the induction of Nav1.3 may be one of the common responses of axotomized DRG neurons without a direct relationship to NGF/GDNF supply. (c) 2008 Wiley-Liss, Inc.

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

Science.gov (United States)

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

Differential expression of ATP7A, ATP7B and CTR1 in adult rat dorsal root ganglion tissue

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Ip Virginia

2010-09-01

Full Text Available Abstract Background ATP7A, ATP7B and CTR1 are metal transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG tissue and their role in platinum-induced neurotoxicity are unknown. To investigate the DRG expression of ATP7A, ATP7B and CTR1, lumbar DRG and reference tissues were collected for real time quantitative PCR, RT-PCR, immunohistochemistry and Western blot analysis from healthy control adult rats or from animals treated with intraperitoneal oxaliplatin (1.85 mg/kg or drug vehicle twice weekly for 8 weeks. Results In DRG tissue from healthy control animals, ATP7A mRNA was clearly detectable at levels similar to those found in the brain and spinal cord, and intense ATP7A immunoreactivity was localised to the cytoplasm of cell bodies of smaller DRG neurons without staining of satellite cells, nerve fibres or co-localisation with phosphorylated heavy neurofilament subunit (pNF-H. High levels of CTR1 mRNA were detected in all tissues from healthy control animals, and strong CTR1 immunoreactivity was associated with plasma membranes and vesicular cytoplasmic structures of the cell bodies of larger-sized DRG neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 had distinct cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non

Identification of key genes and pathways associated with neuropathic pain in uninjured dorsal root ganglion by using bioinformatic analysis

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Chen CJ

2017-11-01

Full Text Available Chao-Jin Chen,* De-Zhao Liu,* Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL by using bioinformatic analysis.Materials and methods: The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI network and module analysis. Real-time polymerase chain reaction (PCR and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.Results: A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were

Hydrodynamic function of dorsal fins in spiny dogfish and bamboo sharks during steady swimming.

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Maia, Anabela; Lauder, George V; Wilga, Cheryl D

2017-11-01

A key feature of fish functional design is the presence of multiple fins that allow thrust vectoring and redirection of fluid momentum to contribute to both steady swimming and maneuvering. A number of previous studies have analyzed the function of dorsal fins in teleost fishes in this context, but the hydrodynamic function of dorsal fins in freely swimming sharks has not been analyzed, despite the potential for differential functional roles between the anterior and posterior dorsal fins. Previous anatomical research has suggested a primarily stabilizing role for shark dorsal fins. We evaluated the generality of this hypothesis by using time-resolved particle image velocimetry to record water flow patterns in the wake of both the anterior and posterior dorsal fins in two species of freely swimming sharks: bamboo sharks ( Chiloscyllium plagiosum ) and spiny dogfish ( Squalus acanthias ). Cross-correlation analysis of consecutive images was used to calculate stroke-averaged mean longitudinal and lateral velocity components, and vorticity. In spiny dogfish, we observed a velocity deficit in the wake of the first dorsal fin and flow acceleration behind the second dorsal fin, indicating that the first dorsal fin experiences net drag while the second dorsal fin can aid in propulsion. In contrast, the wake of both dorsal fins in bamboo sharks displayed increased net flow velocity in the majority of trials, reflecting a thrust contribution to steady swimming. In bamboo sharks, fluid flow in the wake of the second dorsal fin had higher absolute average velocity than that for first dorsal fin, and this may result from a positive vortex interaction between the first and second dorsal fins. These data suggest that the first dorsal fin in spiny dogfish has primarily a stabilizing function, while the second dorsal fin has a propulsive function. In bamboo sharks, both dorsal fins can contribute thrust and should be considered as propulsive adjuncts to the body during steady

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome

DEFF Research Database (Denmark)

Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R O

2016-01-01

BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df...... displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice...

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome

DEFF Research Database (Denmark)

Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R O

2017-01-01

Background: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. Methods: We present a new mouse model (Df...... displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice...

The sea anemone Bunodosoma caissarum toxin BcIII modulates the sodium current kinetics of rat dorsal root ganglia neurons and is displaced in a voltage-dependent manner.

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Salceda, Emilio; López, Omar; Zaharenko, André J; Garateix, Anoland; Soto, Enrique

2010-03-01

Sea anemone toxins bind to site 3 of the sodium channels, which is partially formed by the extracellular linker connecting S3 and S4 segments of domain IV, slowing down the inactivation process. In this work we have characterized the actions of BcIII, a sea anemone polypeptide toxin isolated from Bunodosoma caissarum, on neuronal sodium currents using the patch clamp technique. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study (n=65). The main effects of BcIII were a concentration-dependent increase in the sodium current inactivation time course (IC(50)=2.8 microM) as well as an increase in the current peak amplitude. BcIII did not modify the voltage at which 50% of the channels are activated or inactivated, nor the reversal potential of sodium current. BcIII shows a voltage-dependent action. A progressive acceleration of sodium current fast inactivation with longer conditioning pulses was observed, which was steeper as more depolarizing were the prepulses. The same was observed for other two anemone toxins (CgNa, from Condylactis gigantea and ATX-II, from Anemonia viridis). These results suggest that the binding affinity of sea anemone toxins may be reduced in a voltage-dependent manner, as has been described for alpha-scorpion toxins. (c) 2009 Elsevier Inc. All rights reserved.

Genetically Engineered Mouse Model of Diffuse Intrinsic Pontine Glioma as a Preclinical Tool

Science.gov (United States)

2014-11-01

www.actaneurocomms.org/content/2/1/134N-Myc and Hedgehog [17], MYCN, silent, and H3-K27M [10] or H3-K27M and wildtype [6]. Together, these classi...pons, and as there are significant differences between mouse and human brainstem anatomy , we can- not be certain that the dorsal Nestin+/Pax3...Fisher PG, Weissman IL, Rowitch DH, Vogel H, Wong AJ, Beachy PA (2011) Hedgehog -responsive candidate cell of origin for diffuse intrinsic pontine glioma

A combined electrophysiological and morphological study of neuropeptide Y?expressing inhibitory interneurons in the spinal dorsal horn of the mouse

OpenAIRE

Iwagaki, Noboru; Ganley, Robert P.; Dickie, Allen C.; Polg?r, Erika; Hughes, David I.; Del Rio, Patricia; Revina, Yulia; Watanabe, Masahiko; Todd, Andrew J.; Riddell, John S.

2015-01-01

Abstract The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We th...

Opposing dorsal/ventral stream dynamics during figure-ground segregation.

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Wokke, Martijn E; Scholte, H Steven; Lamme, Victor A F

2014-02-01

The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist between the dorsal and the ventral stream. Here, we used TMS and concurrent EEG recordings to explore these interactions between the dorsal and ventral stream during figure-ground segregation. In two separate experiments, we used repetitive TMS and single-pulse TMS to disrupt processing in the dorsal (V5/HMT⁺) and the ventral (lateral occipital area) stream during a motion-defined figure discrimination task. We presented stimuli that made it possible to differentiate between relatively low-level (figure boundary detection) from higher-level (surface segregation) processing steps during figure-ground segregation. Results show that disruption of V5/HMT⁺ impaired performance related to surface segregation; this effect was mainly found when V5/HMT⁺ was perturbed in an early time window (100 msec) after stimulus presentation. Surprisingly, disruption of the lateral occipital area resulted in increased performance scores and enhanced neural correlates of surface segregation. This facilitatory effect was also mainly found in an early time window (100 msec) after stimulus presentation. These results suggest a "push-pull" interaction in which dorsal and ventral extrastriate areas are being recruited or inhibited depending on stimulus category and task demands.

Effect of interleukin-4 on orthodontic tooth movement and associated root resorption.

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Hakami, Zaki; Kitaura, Hideki; Kimura, Keisuke; Ishida, Masahiko; Sugisawa, Haruki; Ida, Hiroto; Jafari, Saeed; Takano-Yamamoto, Teruko

2015-02-01

Interleukin-4 (IL-4) is a recognized immunomodulatory cytokine that regulates bone homeostasis. However, the influence of IL-4 on orthodontic tooth movement (OTM) and subsequent root resorption is still unknown. Therefore, the purpose of this study was to investigate the effect of IL-4 on tooth movement and its associated root resorption in a mouse model. The maxillary first molars of four male mice for each experimental group were subjected to mesial force by a nickel titanium coil spring for 12 days. Control mice were not given appliances and injections. Varying doses of IL-4 were injected locally, adjacent to the first molar. Two sets of experiments were designed. The first set was composed of three groups: the control, treatment with phosphate-buffered saline (PBS), or 1.5 µg/day of IL-4. The second set was composed of five groups: the control, treatment with 0 (PBS only), 0.015, 0.15, or 1.5 µg/day of IL-4. The distance of OTM was measured and tartrate-resistant acid phosphatase positive cells along the loaded alveolar bone and root surface were identified. The root resorption associated with OTM was evaluated by a scanning electron microscope. The amount of OTM and the number of osteoclasts were significantly decreased in the IL-4-treated mice. Moreover, IL-4 significantly suppressed force-induced odontoclasts and root resorption. IL-4 inhibits tooth movement and prevents root resorption in the mouse model. These results suggest that IL-4 could be used as a useful adjunct to regulate the extent of OTM and also to control root resorption. © The Author 2014. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Periostite metacarpiana dorsal: incidência e fatores pré-disponentes

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Flávio Gomes de Oliveira

2006-04-01

Full Text Available Forty two 2-year-old thoroughbreds were examined clinically at intervals of 15 days during their training for the first race to determine the incidence and the predisposing factors of dorsal metacarpal disease. During the first year 25 horses were followed during 2 months and in the second year the follow up was done for 4 months in 17 . Horses' data like gender, average speed, speed exercise work and trainer were also collected. Dorsal metacarpal disease was diagnosed in 28% and 70,6% of the 2 year-old thoroughbreds in the first and second year of the study, respectively. Total incidence was 45%. The incidence and average speed was not affected by gender. The average speed achieved by affected and none affected horses remained between 16 and 18m/s. On 500 and 700m speed exercise, the average speed of affected horses was higher than of none affected ones (p<0,05. Ten out of 19 horses showed dorsal metacarpal disease signs at the distance of 700m. There was significant difference between trainers regarding the incidence of dorsal metacarpal disease and average speed of their horses. 2-year-olds under care of trainers whose horses had the highest incidence o dorsal metacarpal disease also were the fastest one's. Therefore, fast speed associated with longer distances (700m and trainer are factors that predispose young horses to dorsal metacarpal disease.

Expression of bone morphogenetic proteins and Msx genes during root formation.

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Yamashiro, T; Tummers, M; Thesleff, I

2003-03-01

Like crown development, root formation is also regulated by interactions between epithelial and mesenchymml tissues. Bone morphogenetic proteins (BMPs), together with the transcription factors Msx1 and Msx2, play important roles in these interactions during early tooth morphogenesis. To investigate the involvement of this signaling pathway in root development, we analyzed the expression patterns of Bmp2, Bmp3, Bmp4, and Bmp7 as well as Msx1 and Msx2 in the roots of mouse molars. Bmp4 was expressed in the apical mesenchyme and Msx2 in the root sheath. However, Bmps were not detected in the root sheath epithelium, and Msx transcripts were absent from the underlying mesenchyme. These findings indicate that this Bmp signaling pathway, required for tooth initiation, does not regulate root development, but we suggest that root shape may be regulated by a mechanism similar to that regulating crown shape in cap-stage tooth germs. Msx2 expression continued in the epithelial cell rests of Malassez, and the nearby cementoblasts intensely expressed Bmp3, which may regulate some functions of the fragmented epithelium.

Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

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Norio Takata

Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

Predicting Early Reading Skills from Pre-Reading Measures of Dorsal Stream Functioning

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Kevan, Alison; Pammer, Kristen

2009-01-01

It is well documented that good reading skills may be dependent upon adequate dorsal stream processing. However, the degree to which dorsal stream deficits play a causal role in reading failure has not been established. This study used coherent motion and visual frequency doubling to examine whether dorsal stream sensitivity measured before the…

The human dorsal action control system develops in the absence of vision.

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Fiehler, Katja; Burke, Michael; Bien, Siegfried; Röder, Brigitte; Rösler, Frank

2009-01-01

The primate dorsal pathway has been proposed to compute vision for action. Although recent findings suggest that dorsal pathway structures contribute to somatosensory action control as well, it is yet not clear whether or not the development of dorsal pathway functions depends on early visual experience. Using functional magnetic resonance imaging, we investigated the pattern of cortical activation in congenitally blind and matched blindfolded sighted adults while performing kinesthetically guided hand movements. Congenitally blind adults activated similar dorsal pathway structures as sighted controls. Group-specific activations were found in the extrastriate cortex and the auditory cortex for congenitally blind humans and in the precuneus and the presupplementary motor area for sighted humans. Dorsal pathway activity was in addition observed for working memory maintenance of kinesthetic movement information in both groups. Thus, the results suggest that dorsal pathway functions develop in the absence of vision. This favors the idea of a general mechanism of movement control that operates regardless of the sensory input modality. Group differences in cortical activation patterns imply different movement control strategies as a function of visual experience.

Diffusion-weighted magnetic resonance imaging of symptomatic nerve root of patients with lumbar disk herniation

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Eguchi, Yawara; Ohtori, Seiji; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Munetaka; Orita, Sumihisa; Kamoda, Hiroto; Arai, Gen; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Ochiai, Nobuyasu; Kishida, Shunji; Inoue, Gen; Takahashi, Kazuhisa [Chiba University, Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba (Japan); Masuda, Yoshitada; Ochi, Shigehiro; Kikawa, Takashi [Chiba University Hospital, Department of Radiology, Chiba (Japan); Toyone, Tomoaki [Teikyo University Chiba Medical Center, Department of Orthopaedic Surgery, Chiba (Japan); Takaso, Masashi [Kitasato University, Department of Orthopaedic Surgery, School of Medicine, Sagamihara City, Kanagawa (Japan); Aoki, Yasuchika [Chiba Rosai Hospital, Department of Orthopedic Surgery, Ichihara, Chiba (Japan)

2011-09-15

Diffusion-weighted imaging (DWI) can provide valuable structural information that may be useful for evaluating pathological changes of the lumbar nerve root. Diffusion-weighted magnetic resonance (MR) neurography has recently been introduced as an alternative way to visualize nerves, but to date, quantitative DWI and MR neurography have not been applied to evaluate the pathology of lumbar nerve roots. Our purpose was to visualize lumbar nerve roots and to analyze their morphology by MR neurography, and to measure the apparent diffusion coefficient (ADC) of lumbar nerve roots compressed by herniated disks using 1.5-T MR imaging. Ten consecutive patients (median age, 48.0 and range, 20-72 years) with monoradicular symptoms caused by a lumbar herniated disk and 14 healthy volunteers were studied. Regions of interests were placed on the lumbar roots at dorsal root ganglia (DRG) and distal spinal nerves on DWI to quantify mean ADC values. The spinal nerve roots were also visualized by MR neurography. In the patients, mean ADC values were significantly greater in the compressed DRG and distal spinal nerves than in intact nerves. MR neurography also showed abnormalities such as nerve swelling at and below the compression in the symptomatic nerve root. Increased ADC values were considered to be because of edema and Wallerian degeneration of compressed nerve roots. DWI is a potential tool for analysis of the pathophysiology of lumbar nerve roots compressed by herniated disks. (orig.)

Diffusion-weighted magnetic resonance imaging of symptomatic nerve root of patients with lumbar disk herniation

International Nuclear Information System (INIS)

Eguchi, Yawara; Ohtori, Seiji; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Munetaka; Orita, Sumihisa; Kamoda, Hiroto; Arai, Gen; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Ochiai, Nobuyasu; Kishida, Shunji; Inoue, Gen; Takahashi, Kazuhisa; Masuda, Yoshitada; Ochi, Shigehiro; Kikawa, Takashi; Toyone, Tomoaki; Takaso, Masashi; Aoki, Yasuchika

2011-01-01

Diffusion-weighted imaging (DWI) can provide valuable structural information that may be useful for evaluating pathological changes of the lumbar nerve root. Diffusion-weighted magnetic resonance (MR) neurography has recently been introduced as an alternative way to visualize nerves, but to date, quantitative DWI and MR neurography have not been applied to evaluate the pathology of lumbar nerve roots. Our purpose was to visualize lumbar nerve roots and to analyze their morphology by MR neurography, and to measure the apparent diffusion coefficient (ADC) of lumbar nerve roots compressed by herniated disks using 1.5-T MR imaging. Ten consecutive patients (median age, 48.0 and range, 20-72 years) with monoradicular symptoms caused by a lumbar herniated disk and 14 healthy volunteers were studied. Regions of interests were placed on the lumbar roots at dorsal root ganglia (DRG) and distal spinal nerves on DWI to quantify mean ADC values. The spinal nerve roots were also visualized by MR neurography. In the patients, mean ADC values were significantly greater in the compressed DRG and distal spinal nerves than in intact nerves. MR neurography also showed abnormalities such as nerve swelling at and below the compression in the symptomatic nerve root. Increased ADC values were considered to be because of edema and Wallerian degeneration of compressed nerve roots. DWI is a potential tool for analysis of the pathophysiology of lumbar nerve roots compressed by herniated disks. (orig.)

Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

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Shigeo Hasegawa

Full Text Available BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2 (cPLA(2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2 activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha and interleukin-1beta (IL-1beta expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

Thermal effects of dorsal head immersion in cold water on nonshivering humans.

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Giesbrecht, Gordon G; Lockhart, Tamara L; Bristow, Gerald K; Steinman, Allan M

2005-11-01

Personal floatation devices maintain either a semirecumbent flotation posture with the head and upper chest out of the water or a horizontal flotation posture with the dorsal head and whole body immersed. The contribution of dorsal head and upper chest immersion to core cooling in cold water was isolated when the confounding effect of shivering heat production was inhibited with meperidine (Demerol, 2.5 mg/kg). Six male volunteers were immersed four times for up to 60 min, or until esophageal temperature = 34 degrees C. An insulated hoodless dry suit or two different personal floatation devices were used to create four conditions: 1) body insulated, head out; 2) body insulated, dorsal head immersed; 3) body exposed, head (and upper chest) out; and 4) body exposed, dorsal head (and upper chest) immersed. When the body was insulated, dorsal head immersion did not affect core cooling rate (1.1 degrees C/h) compared with head-out conditions (0.7 degrees C/h). When the body was exposed, however, the rate of core cooling increased by 40% from 3.6 degrees C/h with the head out to 5.0 degrees C/h with the dorsal head and upper chest immersed (P immersed (approximately 10%). The exaggerated core cooling during dorsal head immersion (40% increase) may result from the extra heat loss affecting a smaller thermal core due to intense thermal stimulation of the body and head and resultant peripheral vasoconstriction. Dorsal head and upper chest immersion in cold water increases the rate of core cooling and decreases potential survival time.

Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

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Lyu C

2017-08-01

Full Text Available Chuang Lyu,1,2 Gong-Wei Lyu,3 Aurora Martinez,4 Tie-Jun Sten Shi4 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China; 2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; 3Department of Neurology, 1st Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Biomedicine, University of Bergen, Bergen, Norway Background: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods: A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results: There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion: Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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Karina H. Solís

2017-12-01

Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

Differentiation state determines neural effects on microvascular endothelial cells

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Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

2012-01-01

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

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Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

2018-03-09

This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

Dorsal buccal mucosal graft urethroplasty for anterior urethral stricture by Asopa technique.

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Pisapati, V L N Murthy; Paturi, Srimannarayana; Bethu, Suresh; Jada, Srikanth; Chilumu, Ramreddy; Devraj, Rahul; Reddy, Bhargava; Sriramoju, Vidyasagar

2009-07-01

Buccal mucosal graft (BMG) substitution urethroplasty has become popular in the management of intractable anterior urethral strictures with good results. Excellent long-term results have been reported by both dorsal and ventral onlay techniques. Asopa reported a successful technique for dorsal placement of BMG in long anterior urethral strictures through a ventral sagittal approach. To evaluate prospectively the results and advantages of dorsal BMG urethroplasty for recurrent anterior urethral strictures by a ventral sagittal urethrotomy approach (Asopa technique). From December 2002 to December 2007, a total of 58 men underwent dorsal BMG urethroplasty by a ventral sagittal urethrotomy approach for recurrent urethral strictures. Forty-five of these patients with a follow-up period of 12-60 mo were prospectively evaluated, and the results were analysed. The urethra was split twice at the site of the stricture both ventrally and dorsally without mobilising it from its bed, and the buccal mucosal graft was secured in the dorsal urethral defect. The urethra was then retubularised in one stage. The overall results were good (87%), with a mean follow-up period of 42 mo. Seven patients developed minor wound infection, and five patients developed fistulae. There were six recurrences (6:45, 13%) during the follow-up period of 12-60 mo. Two patients with a panurethral stricture and four with bulbar or penobulbar strictures developed recurrences and were managed by optical urethrotomy and self-dilatation. The medium-term results were as good as those reported with the dorsal urethrotomy approach. Long-term results from this and other series are awaited. More randomised trials and meta-analyses are needed to establish this technique as a procedure of choice in future. The ventral sagittal urethrotomy approach is easier to perform than the dorsal urethrotomy approach, has good results, and is especially useful in long anterior urethral strictures.

The issue of ventral versus dorsal approach in bulbar urethral ...

African Journals Online (AJOL)

E. Palminteri

From surgical point of view, the Barbagli Dorsal Grafting by Dor- sal approach [8] gives a good support for the graft; Barbagli stated that his technique offers a wider augmentation than ventral or dorsal grafting using the ventral approach. The good spongiosum covering seems reduce the risk of fistula; in reality there is a ...

bullwinkle and shark regulate dorsal-appendage morphogenesis in Drosophila oogenesis.

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Tran, David H; Berg, Celeste A

2003-12-01

bullwinkle (bwk) regulates embryonic anteroposterior patterning and, through a novel germline-to-soma signal, morphogenesis of the eggshell dorsal appendages. We screened for dominant modifiers of the bullwinkle mooseantler eggshell phenotype and identified shark, which encodes an SH2-domain, ankyrin-repeat tyrosine kinase. At the onset of dorsal-appendage formation, shark is expressed in a punctate pattern in the squamous stretch cells overlying the nurse cells. Confocal microscopy with cell-type-specific markers demonstrates that the stretch cells act as a substrate for the migrating dorsal-appendage-forming cells and extend cellular projections towards them. Mosaic analyses reveal that shark is required in follicle cells for cell migration and chorion deposition. Proper shark RNA expression in the stretch cells requires bwk activity, while restoration of shark expression in the stretch cells suppresses the bwk dorsal-appendage phenotype. These results suggest that shark plays an important downstream role in the bwk-signaling pathway. Candidate testing implicates Src42A in a similar role, suggesting conservation with a vertebrate signaling pathway involving non-receptor tyrosine kinases.

Attention modulates the dorsal striatum response to love stimuli.

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Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

2014-02-01

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

Effects of sciatic nerve transection on glucose uptake in the presence and absence of lactate in the frog dorsal root ganglia and spinal cord

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F Rigon

Full Text Available Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT, which mimics the clinical symptoms of “phantom limb”, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.

Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

Science.gov (United States)

Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

2013-01-01

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

The dorsal thoracic fascia: anatomic significance with clinical applications in reconstructive microsurgery.

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Kim, P S; Gottlieb, J R; Harris, G D; Nagle, D J; Lewis, V L

1987-01-01

The anatomic distribution and potential arterial flow patterns of the circumflex scapular artery were investigated by Microfil injection. These studies demonstrated that the circumflex scapular artery lies within the dorsal thoracic fascia, which plays a significant role in the circulation of the overlying skin and subcutaneous tissue. We conclude that scapular/parascapular flaps are fasciocutaneous flaps, the dorsal thoracic fascia can be transferred as a free flap without its overlying skin and subcutaneous tissue, and intercommunication exists between the myocutaneous perforators of the latissimus dorsi myocutaneous flap and the vascular plexus of the dorsal thoracic fascia. We present microvascular cases in which the vascular properties of the dorsal thoracic fascia facilitated wound closure with free fascia flaps or expanded cutaneous or myocutaneous flaps.

Compound dorsal dislocation of lunate with trapezoid fracture

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Bong-Sung Kim

2016-12-01

Full Text Available We report about a dorsal dislocation of the lunate accompanied by a trapezoid fracture in a 41-year old male patient after a motorcycle accident. The lunate dislocation with no dorsal or volar intercalated segment instability (DISI, VISI was diagnosed by x-ray whereas the trapezoid fracture was only diagnosable by computed tomography. A closed reduction and internal fixation of the lunate by two Kirschner wires was performed, the trapezoid fracture was conservatively treated. Surgery was followed by immobilization, intense physiotherapy and close follow-up. Even though complaints such as swelling and pain subsided during the course of rehabilitation, partial loss of strength and range of motion remained even after 16 months. In conclusion, a conservative treatment of trapezoid fractures seems to be sufficient in most cases. Closed reduction with Kwire fixation led to an overall satisfactory result in our case. For dorsal lunate dislocations in general, open reduction should be performed when close reduction is unsuccessful or DISI/VISI are observed in radiographs after attempted close reduction.

Dissociated repetition deficits in aphasia can reflect flexible interactions between left dorsal and ventral streams and gender-dimorphic architecture of the right dorsal stream.

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Berthier, Marcelo L; Froudist Walsh, Seán; Dávila, Guadalupe; Nabrozidis, Alejandro; Juárez Y Ruiz de Mier, Rocío; Gutiérrez, Antonio; De-Torres, Irene; Ruiz-Cruces, Rafael; Alfaro, Francisco; García-Casares, Natalia

2013-01-01

Assessment of brain-damaged subjects presenting with dissociated repetition deficits after selective injury to either the left dorsal or ventral auditory pathways can provide further insight on their respective roles in verbal repetition. We evaluated repetition performance and its neural correlates using multimodal imaging (anatomical MRI, DTI, fMRI, and(18)FDG-PET) in a female patient with transcortical motor aphasia (TCMA) and in a male patient with conduction aphasia (CA) who had small contiguous but non-overlapping left perisylvian infarctions. Repetition in the TCMA patient was fully preserved except for a mild impairment in nonwords and digits, whereas the CA patient had impaired repetition of nonwords, digits and word triplet lists. Sentence repetition was impaired, but he repeated novel sentences significantly better than clichés. The TCMA patient had tissue damage and reduced metabolism in the left sensorimotor cortex and insula. DTI showed damage to the left temporo-frontal and parieto-frontal segments of the arcuate fasciculus (AF) and part of the left ventral stream together with well-developed right dorsal and ventral streams, as has been reported in more than one-third of females. The CA patient had tissue damage and reduced metabolic activity in the left temporoparietal cortex with additional metabolic decrements in the left frontal lobe. DTI showed damage to the left temporo-parietal and temporo-frontal segments of the AF, but the ventral stream was spared. The direct segment of the AF in the right hemisphere was also absent with only vestigial remains of the other dorsal subcomponents present, as is often found in males. fMRI during word and nonword repetition revealed bilateral perisylvian activation in the TCMA patient suggesting recruitment of spared segments of the left dorsal stream and right dorsal stream with propagation of signals to temporal lobe structures suggesting a compensatory reallocation of resources via the ventral streams. The

Amnioserosa cell constriction but not epidermal actin cable tension autonomously drives dorsal closure.

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Pasakarnis, Laurynas; Frei, Erich; Caussinus, Emmanuel; Affolter, Markus; Brunner, Damian

2016-11-01

Tissue morphogenesis requires coordination of multiple force-producing components. During dorsal closure in fly embryogenesis, an epidermis opening closes. A tensioned epidermal actin/MyosinII cable, which surrounds the opening, produces a force that is thought to combine with another MyosinII force mediating apical constriction of the amnioserosa cells that fill the opening. A model proposing that each force could autonomously drive dorsal closure was recently challenged by a model in which the two forces combine in a ratchet mechanism. Acute force elimination via selective MyosinII depletion in one or the other tissue shows that the amnioserosa tissue autonomously drives dorsal closure while the actin/MyosinII cable cannot. These findings exclude both previous models, although a contribution of the ratchet mechanism at dorsal closure onset remains likely. This shifts the current view of dorsal closure being a combinatorial force-component system to a single tissue-driven closure event.

Complete dorsal pancreatic agenesis and unilateral renal agenesis.

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Moreira, Adriana; Carvalho, André; Portugal, Inês; Jesus, José Miguel

2018-02-01

Dorsal pancreatic agenesis is a very rare congenital anomaly. Unilateral renal agenesis, on the other hand, is a relatively common congenital anomaly, although its etiology is not fully understood. Renal and pancreatic embryologic development appears to be nonrelated. We report a case of a 34-year-old man who was referred to our hospital for evaluation of cholestasis and microalbuminuria. Ultrasound and magnetic resonance imaging examinations showed empty right renal fossa and absence of the pancreatic neck, body, and tail. Our case report is the second case of a dorsal pancreatic agenesis and unilateral renal agenesis in a young male patient.

[Optogenetic activation of dorsal hippocampal astrocytic Rac1 blocks the learning of associative memory].

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Guo, Xiao-Mu; Liao, Zhao-Hui; Tao, Ye-Zheng; Wang, Fei-Fei; Ma, Lan

2017-06-25

Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation. Primary culture of hippocampal astrocytes was infected with the recombinant AAV-PA-Rac1 or AAV-PA-Rac1-C450A. Real-time fluorescence imaging showed that the cell membrane of the astrocyte expressing PA-Rac1 protruded near the light spot, while the astrocyte expressing PA-Rac1-C450A did not. We injected AAV-PA-Rac1 and AAV-PA-Rac1-C450A into dorsal hippocampus to investigate the role of the activation of Rac1 in regulating the associative learning. With optical stimulation, the PA-Rac1 group, rather than the PA-Rac1-C450A group, showed slower learning curve during the fear conditioning compared with the control group, indicating that activating astrocytic Rac1 blocks the formation of contextual memory. Our data suggest that the activation of Rac1 in dorsal hippocampal astrocyte plays an important role in the associative learning.

Attenuation of TRPV1 and TRPV4 Expression and Function in Mouse Inflammatory Pain Models Using Electroacupuncture

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Wei-Hsin Chen

2012-01-01

Full Text Available Although pain is a major human affliction, our understanding of pain mechanisms is limited. TRPV1 (transient receptor potential vanilloid subtype 1 and TRPV4 are two crucial receptors involved in inflammatory pain, but their roles in EA- (electroacupuncture- mediated analgesia are unknown. We injected mice with carrageenan (carra or a complete Freund’s adjuvant (CFA to model inflammatory pain and investigated the analgesic effect of EA using animal behavior tests, immunostaining, Western blotting, and a whole-cell recording technique. The inflammatory pain model mice developed both mechanical and thermal hyperalgesia. Notably, EA at the ST36 acupoint reversed these phenomena, indicating its curative effect in inflammatory pain. The protein levels of TRPV1 and TRPV4 in DRG (dorsal root ganglion neurons were both increased at day 4 after the initiation of inflammatory pain and were attenuated by EA, as demonstrated by immunostaining and Western blot analysis. We verified DRG electrophysiological properties to confirm that EA ameliorated peripheral nerve hyperexcitation. Our results indicated that the AP (action potential threshold, rise time, and fall time, and the percentage and amplitude of TRPV1 and TRPV4 were altered by EA, indicating that EA has an antinociceptive role in inflammatory pain. Our results demonstrate a novel role for EA in regulating TRPV1 and TRPV4 protein expression and nerve excitation in mouse inflammatory pain models.

Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia.

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Nuglozeh, Edem

2017-07-01

compelled us to work at the level of hemizygosity. The histological characterisation of left ventricle shows cardiac hypertrophy together with decrease in body mass and alopecia, this compared to the wild type. The immunohistochemical staining of aorta root showed hyperplasia with increased expression and colocalisation of renin and CTGF demonstrating that CTGF may be involved in vascular tone control. Genetic engineering is a noble avenue to investigate the function of new or existing genes. Our data have shown that CTGF transgenic mouse has cardiac and aorta root hypertrophy and abnormal renin accumulation in aorta root as compared to the wild-type animals. The transgenic animals developed alopecia and lean body mass adding two new functions on pre-existing CTGF multiple functions.

Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

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Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

2015-08-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

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Falci, Scott; Indeck, Charlotte; Barnkow, Dave

2018-06-01

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique

Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain.

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Xianxun Chi

Full Text Available The vast majority of people living with human immunodeficiency virus type 1 (HIV-1 have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP, and an increase in the resistance at threshold (R(Th. Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5 activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs of DRGs. However, Tat-mediated actions on the rheobase and R(Th were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.

Effects of electroacupuncture at 2 and 100 Hz on rat type 2 diabetic neuropathic pain and hyperalgesia-related protein expression in the dorsal root ganglion.

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He, Xiao-Fen; Wei, Jun-Jun; Shou, Sheng-Yun; Fang, Jian-Qiao; Jiang, Yong-Liang

To investigate the analgesic effects of electroacupuncture (EA) at 2 and 100 Hz on type 2 diabetic neuropathic pain (DNP) and on the expressions of the P2X3 receptor and calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). Rat type 2 DNP was induced by a high calorie and high sugar diet fed for 7 weeks, plus a single intraperitoneal injection of streptozotocin (STZ) after 5 weeks. EA at 2 and 100 Hz was carried out once every day after 7 weeks for 7 consecutive days. Body weight, serum fasting insulin (FINS), fasting blood glucose (FBG), insulin sensitivity index (ISI), and paw withdrawal latency (PWL) were measured. The expressions of L4-L6 DRG P2X3 receptors and CGRP were assessed by immunofluorescence. Type 2 DNP was successfully induced as shown by the increased body weight, FINS, and FBG, as well as the reduced ISI and PWL. Expressions of P2X3 receptors and CGRP in L4-L6 DRGs increased. EA at both 2 and 100 Hz relieved type 2 DNP, but the analgesic effect of EA was stronger at 2 Hz. P2X3 receptor expression decreased in L4-L6 DRGs following EA at 2 Hz and in L5 and L6 DRGs following EA at 100 Hz. EA at both 2 and 100 Hz down-regulated CGRP overexpression in L4-L6 DRGs. These findings indicate that EA at 2 Hz is a good option for the management of type 2 DNP. The EA effect may be related to its down-regulation of the overexpressions of the DRG P2X3 receptors and CGRP in this condition.

Dorsal Phalloplasty to Preserve Penis Length after Penile Prosthesis Implantation

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Osama Shaeer

2017-03-01

Full Text Available Objectives: Following penile prosthesis implantation (PPI, patients may complain of a decrease in visible penis length. A dorsal phalloplasty defines the penopubic junction by tacking pubic skin to the pubis, revealing the base of the penis. This study aimed to evaluate the efficacy of a dorsal phalloplasty in increasing the visible penis length following PPI. Methods: An inflatable penile prosthesis was implanted in 13 patients with severe erectile dysfunction (ED at the Kamal Shaeer Hospital, Cairo, Egypt, from January 2013 to May 2014. During the surgery, nonabsorbable tacking sutures were used to pin the pubic skin to the pubis through the same penoscrotal incision. Intraoperative penis length was measured before and after the dorsal phalloplasty. Overall patient satisfaction was measured on a 5-point rating scale and patients were requested to subjectively compare their postoperative penis length with memories of their penis length before the onset of ED. Results: Intraoperatively, the dorsal phalloplasty increased the visible length of the erect penis by an average of 25.6%. The average length before and after tacking was 10.2 ± 2.9 cm and 13.7 ± 2.8 cm, respectively (P <0.002. Postoperatively, seven patients (53.8% reported a longer penis, five patients (38.5% reported no change in length and one patient (7.7% reported a slightly shorter penis. The mean overall patient satisfaction score was 4.9 ± 0.3. None of the patients developed postoperative complications. Conclusion: A dorsal phalloplasty during PPI is an effective method of increasing visible penis length, therefore minimising the impression of a shorter penis after implantation.

Agenesis of the dorsal mesentery presenting in an adolescent

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Anith Chacko

2013-03-01

Full Text Available Agenesis of the dorsal mesentery is a rare occurrence that usually presents in children. It is associated with proximal small bowel malrotation as well as high jejunal atresia with discontinuity of the small bowel. We present a case report of an adolescent presenting with clinical features of proximal small bowel obstruction (confirmed on imaging as well as acute pancreatitis. At laparotomy, he was found to have no dorsal mesentery, without small bowel atresia, and the duodenum was fixed to the posterior abdominal wall. The patient recovered well and remained symptom-free.

[Posttrial injections of corticosterone in dorsal hippocampus of the BALB/c mouse facilitate extinction of appetitive operant conditioning in the Skinner box].

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Micheau, J; Destrade, C; Soumireu-Mourat, B

1982-06-28

Corticosterone was injected bilaterally into the dorsal hippocampus of BALB/c Mice immediately after the first extinction session of an operant conditioning in a Skinner box. Compared with the control animals the Mice that received 1 or 0.1 microgram corticosterone exhibited 24 hrs. later, faster extinction of this conditioning. With a 0.01 microgram dose of corticosterone in each hippocampus we obtained an accelerated extinction during the session. These data suggest that corticosterone modulates hippocampal mechanisms involved in memory processes.

Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

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Steven M. Horton

2017-11-01

Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

The presence of nuclear cactus in the early Drosophila embryo may extend the dynamic range of the dorsal gradient.

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Michael D O'Connell

2015-04-01

Full Text Available In a developing embryo, the spatial distribution of a signaling molecule, or a morphogen gradient, has been hypothesized to carry positional information to pattern tissues. Recent measurements of morphogen distribution have allowed us to subject this hypothesis to rigorous physical testing. In the early Drosophila embryo, measurements of the morphogen Dorsal, which is a transcription factor responsible for initiating the earliest zygotic patterns along the dorsal-ventral axis, have revealed a gradient that is too narrow to pattern the entire axis. In this study, we use a mathematical model of Dorsal dynamics, fit to experimental data, to determine the ability of the Dorsal gradient to regulate gene expression across the entire dorsal-ventral axis. We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns. First, we assume that Cactus, an inhibitor that binds to Dorsal and prevents it from entering the nuclei, must itself be present in the nuclei. And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal. Our model explains the dynamic behavior of the Dorsal gradient at lateral and dorsal positions of the embryo, the ability of Dorsal to regulate gene expression across the entire dorsal-ventral axis, and the robustness of gene expression to stochastic effects. Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.

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Tinaz, Sule; Malone, Patrick; Hallett, Mark; Horovitz, Silvina G

2015-08-01

The mid-posterior part of the insula is involved in processing bodily sensations and urges and is activated during tic generation in Tourette syndrome. The dorsal anterior part of the insula, however, integrates sensory and emotional information with cognitive valuation and is implicated in interoception. The right dorsal anterior insula also participates in urge suppression in healthy subjects. This study examined the role of the right dorsal anterior insula in the urge to tic in Tourette syndrome. Resting-state functional magnetic resonance imaging was performed in 13 adult Tourette patients and 13 matched controls. The role of the right dorsal anterior insula within the urge-tic network was investigated using graph theory-based neural network analysis. The functional connectivity of the right dorsal anterior insula was also correlated with urge and tic severity. Even though the patients did not exhibit any overt tics, the right dorsal anterior insula demonstrated higher connectivity, especially with the frontostriatal nodes of the urge-tic network in patients compared with controls. The functional connectivity between the right dorsal anterior insula and bilateral supplementary motor area also correlated positively with urge severity in patients. These results suggest that the right dorsal anterior insula is part of the urge-tic network and could influence the urge- and tic-related cortico-striato-thalamic regions even during rest in Tourette syndrome. It might be responsible for heightened awareness of bodily sensations generating premonitory urges in Tourette syndrome. © 2015 International Parkinson and Movement Disorder Society.

Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

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Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

2012-01-01

The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a

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Jennifer R. Deuis; Zoltan Dekan; Joshua S. Wingerd; Jennifer J. Smith; Nehan R. Munasinghe; Rebecca F. Bhola; Wendy L. Imlach; Volker Herzig; David A. Armstrong; K. Johan Rosengren; Frank Bosmans; Stephen G. Waxman; Sulayman D. Dib-Hajj; Pierre Escoubas; Michael S. Minett

2017-01-01

Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, ?-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9?nM) with at least 40?1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed...

NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

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Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

2016-01-01

Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

Basal Cell Carcinoma of the Dorsal Hand: An Update and Comprehensive Review of the Literature.

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Loh, Tiffany Y; Rubin, Ashley G; Brian Jiang, Shang I

2016-04-01

Excessive ultraviolet radiation (UVR) exposure is the primary predisposing factor for basal cell carcinoma (BCC). However, surprisingly, BCCs occur very rarely on the dorsal hand, which is subject to intense sun exposure, and their infrequent presentation in this location suggests that other factors besides UVR may play a role in BCC pathogenesis. Because dorsal hand BCCs are uncommon, knowledge of their characteristics is limited, and more data are needed to describe their clinical presentation and treatment. To perform an updated review of the literature on the management of dorsal hand BCCs. The authors conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal hand," "basal cell carcinoma hand," and "basal cell carcinoma finger," and "basal cell carcinoma thumb." The authors identified 176 cases of dorsal hand BCCs in the literature, 120 of which had sufficient data for analysis. Only 4 cases were treated with Mohs micrographic surgery (MMS). The authors present 14 additional cases of dorsal hand BCCs treated with MMS. Basal cell carcinomas on the dorsal hand occur infrequently, and potential risk factors include being a male of white descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment method.

Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

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Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

2017-01-01

Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.

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Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E

2014-05-01

Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

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Kurachi, M; Aihara, H

1984-09-01

The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

Two different streams form the dorsal visual system: anatomy and functions.

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Rizzolatti, Giacomo; Matelli, Massimo

2003-11-01

There are two radically different views on the functional role of the dorsal visual stream. One considers it as a system involved in space perception. The other is of a system that codes visual information for action organization. On the basis of new anatomical data and a reconsideration of previous functional and clinical data, we propose that the dorsal stream and its recipient parietal areas form two distinct functional systems: the dorso-dorsal stream (d-d stream) and the ventro-dorsal stream (v-d stream). The d-d stream is formed by area V6 (main d-d extrastriate visual node) and areas V6A and MIP of the superior parietal lobule. Its major functional role is the control of actions "on line". Its damage leads to optic ataxia. The v-d stream is formed by area MT (main v-d extrastriate visual node) and by the visual areas of the inferior parietal lobule. As the d-d stream, v-d stream is responsible for action organization. It, however, also plays a crucial role in space perception and action understanding. The putative mechanisms linking action and perception in the v-d stream is discussed.

The evolution of the dorsal thalamus of jawed vertebrates, including mammals: cladistic analysis and a new hypothesis.

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Butler, A B

1994-01-01

The evolution of the dorsal thalamus in various vertebrate lineages of jawed vertebrates has been an enigma, partly due to two prevalent misconceptions: the belief that the multitude of nuclei in the dorsal thalamus of mammals could be meaningfully compared neither with the relatively few nuclei in the dorsal thalamus of anamniotes nor with the intermediate number of dorsal thalamic nuclei of other amniotes and a definition of the dorsal thalamus that too narrowly focused on the features of the dorsal thalamus of mammals. The cladistic analysis carried out here allows us to recognize which features are plesiomorphic and which apomorphic for the dorsal thalamus of jawed vertebrates and to then reconstruct the major changes that have occurred in the dorsal thalamus over evolution. Embryological data examined in the context of Von Baerian theory (embryos of later-descendant species resemble the embryos of earlier-descendant species to the point of their divergence) supports a new 'Dual Elaboration Hypothesis' of dorsal thalamic evolution generated from this cladistic analysis. From the morphotype for an early stage in the embryological development of the dorsal thalamus of jawed vertebrates, the divergent, sequential stages of the development of the dorsal thalamus are derived for each major radiation and compared. The new hypothesis holds that the dorsal thalamus comprises two basic divisions--the collothalamus and the lemnothalamus--that receive their predominant input from the midbrain roof and (plesiomorphically) from lemniscal pathways, including the optic tract, respectively. Where present, the collothalamic, midbrain-sensory relay nuclei are homologous to each other in all vertebrate radiations as discrete nuclei. Within the lemnothalamus, the dorsal lateral geniculate nucleus of mammals and the dorsal lateral optic nucleus of non-synapsid amniotes (diapsid reptiles, birds and turtles) are homologous as discrete nuclei; most or all of the ventral nuclear group

Assessing dorsal scute microchemistry for reconstruction of shortnose sturgeon life histories

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Altenritter, Matthew E.; Kinnison, Michael T.; Zydlewski, Gayle B.; Secor, David H.; Zydlewski, Joseph D.

2015-01-01

The imperiled status of sturgeons worldwide places priority on the identification and protection of critical habitats. We assessed the micro-structural and micro-chemical scope for a novel calcified structure, dorsal scutes, to be used for reconstruction of past habitat use and group separation in shortnose sturgeon (Acipenser brevirostrum). Dorsal scutes contained a dual-layered structure composed of a thin multi-layered translucent zone lying dorsally above a thicker multi-layered zone. Banding in the thick multi-layered zone correlated strongly with pectoral fin spine annuli supporting the presence of chronological structuring that could contain a chemical record of past environmental exposure. Trace element profiles (Sr:Ca), collected using both wavelength dispersive electron microprobe analysis and laser ablation inductively coupled mass spectrometry, suggest scutes record elemental information useful for tracing transitions between freshwater and marine environments. Moreover, mirror-image like Sr:Ca profiles were observed across the dual-zone structuring of the scute that may indicate duplication of the microchemical profile in a single structure. Additional element:calcium ratios measured in natal regions of dorsal scutes (Ba:Ca, Mg:Ca) suggest the potential for further refinement of techniques for identification of river systems of natal origin. In combination, our results provide proof of concept that dorsal scutes possess the necessary properties to be used as structures for reconstructions of past habitat use in sturgeons. Importantly, scutes may be collected non-lethally and with less injury than current structures, like otoliths and fin spines, affording an opportunity for broader application of microchemical techniques.

Selective Radiofrequency Stimulation of the Dorsal Root Ganglion (DRG) as a Method for Predicting Targets for Neuromodulation in Patients With Post Amputation Pain: A Case Series.

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Hunter, Corey W; Yang, Ajax; Davis, Tim

2017-10-01

While spinal cord stimulation (SCS) has established itself as an accepted and validated treatment for neuropathic pain, there are a number of conditions where it has experienced less, long-term success: post amputee pain (PAP) being one of them. Dorsal root ganglion (DRG) stimulation has shown great promise, particularly in conditions where traditional SCS has fallen short. One major difference between DRG stimulation and traditional SCS is the ability to provide focal stimulation over targeted areas. While this may be a contributing factor to its superiority, it can also be a limitation insofar stimulating the wrong DRG(s) can lead to failure. This is particularly relevant in conditions like PAP where neuroplastic maladaptation occurs causing the pain to deviate from expected patterns, thus creating uncertainty and variability in predicting targets for stimulation. We propose selective radiofrequency (RF) stimulation of the DRG as a method for preoperatively predicting targets for neuromodulation in patients with PAP. We present four patients with PAP of the lower extremities. RF stimulation was used to selectively stimulate individual DRG's, creating areas of paresthesias to see which most closely correlated/overlapped with the painful area(s). RF stimulation to the DRG's that resulted in the desirable paresthesia coverage in the residual or the missing limb(s) was recorded as "positive." Trial DRG leads were placed based on the positive RF stimulation findings. In each patient, stimulating one or more DRG(s) produced paresthesias patterns that were contradictory to know dermatomal patterns. Upon completion of a one-week trial all four patients reported 60-90% pain relief, with coverage over the painful areas, and opted for permanent implant. Mapping the DRG via RF stimulation appears to provide improved accuracy for determining lead placement in the setting of PAP where pain patterns are known to deviate from conventional dermatomal mapping. © 2017

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy.

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Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng; Ma, Li

2018-01-01

WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC- β 3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC- β 3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC- β 3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC- β 3 mRNA and protein expression in the diabetic DRG of DPN rats.

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy

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Chengcheng Feng

2018-01-01

Full Text Available WenTong HuoXue Cream (WTHX-Cream has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN. This study investigated the gene and protein expression of the pain-related molecule PLC-β3 in the dorsal root ganglion (DRG of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats and DPN model (78 rats groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC-β3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC-β3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-β3 mRNA and protein expression in the diabetic DRG of DPN rats.

Short-term plasticity in turtle dorsal horn neurons mediated by L-type Ca2+ channels

DEFF Research Database (Denmark)

Russo, R E; Hounsgaard, J

1994-01-01

Windup--the gradual increase of the response--of dorsal horn neurons to repeated activation of primary afferents is an elementary form of short-term plasticity that may mediate central sensitization to pain. In deep dorsal horn neurons of the turtle spinal cord in vitro we report windup of the re......Windup--the gradual increase of the response--of dorsal horn neurons to repeated activation of primary afferents is an elementary form of short-term plasticity that may mediate central sensitization to pain. In deep dorsal horn neurons of the turtle spinal cord in vitro we report windup...

[Disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A case report].

Science.gov (United States)

Arishima, Hidetaka; Kikuta, Ken-ichirou

2011-04-01

We report the case of disseminated metastatic tumor at dorsal surface of medulla oblongata presenting intractable hiccups. A 73-year-old man has a history of for metastatic lung tumor of the left tempral lobe. Although 3 surgeries and 4 radiotherapies were performed in the last 8 years, residual tumor grew slowly. He presented with intractable hiccups. His hiccups continued for 30 minutes, sometimes for 3 hours with obstruction of eating. Contrast-enhanced Magnetic resonance (MR) imaging demonstrated the dissemination of metastatic lung tumor at dorsal surface of medulla oblongata and ventral surface of midbrain. Some literatures reported the patients with intractable hiccups caused by dorsal medullary lesions. Therefore, we thought that the small disseminated tumor at dorsal surface of medulla oblongata caused the hiccups. Evaluation of dorsal medullay area by MR imaging is important to reveal the cause of intractable hiccups.

Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

Science.gov (United States)

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

2011-01-01

Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain. PMID:21389306

Elevated Expression of Fractalkine (CX3CL1 and Fractalkine Receptor (CX3CR1 in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain

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Wenjun Zhu

2013-01-01

Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP. Molecular signaling through fractalkine (CX3CL1, a nociceptive chemokine, via its receptor (CX3CR1 is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG and spinal cord (SC 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG /SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.

CT-guided cervical nerve root injections: comparing the immediate post-injection anesthetic-related effects of the transforaminal injection with a new indirect technique

International Nuclear Information System (INIS)

Sutter, Reto; Pfirrmann, Christian W.A.; Peterson, Cynthia K.; Zanetti, Marco; Hodler, Juerg

2011-01-01

To describe an ''indirect'' cervical nerve root injection technique with a dorsal approach that should carry less inherent risk than the ''direct'' cervical transforaminal injection approach, and to compare the immediate post-injection results of the two procedures. The indirect and direct cervical nerve root injection procedures are described in detail. Fifty-three consecutive patients receiving the indirect nerve root injections during 2009-2010 were age- and gender-matched to 53 patients who underwent direct transforaminal nerve root injections performed in 2006. Pain level data were collected immediately before and 20-30 min after each procedure. The percentages of pain change in the two groups were compared using the unpaired Student's t test. Fifty-two men (mean age 49) and 54 women (mean age 55) were included. The mean percentage of pain reduction for patients receiving indirect nerve root injections was 38.4% and for those undergoing the direct nerve root injections approach it was 43.2%. This was not significantly different (P = 0.455). No immediate or late adverse effects were reported after either injection procedure. The indirect cervical nerve root injection procedure is a potentially safer alternative to direct cervical transforaminal nerve root injections. The short-term pain reduction is similar using the two injection methods. (orig.)

Dorsal onlay vaginal graft urethroplasty for female urethral stricture

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Manmeet Singh

2013-01-01

Full Text Available Introduction: Female urethral stricture is an underdiagnosed and overlooked cause of female bladder outlet obstruction. The possible etiologies may be infection, prior dilation, difficult catheterization with subsequent fibrosis, urethral surgery, trauma, or idiopathic. We present our technique and results of dorsal onlay full thickness vaginal graft urethroplasty for female urethral stricture. Materials and Methods: A retrospective review was performed on 16 female patients with mid-urethral stricture who underwent dorsal onlay vaginal graft urethroplasty from January 2007 to June 2011.Of these, 13 patients had previously undergone multiple Hegar dilatations, three had previous internal urethrotomies. The preoperative work up included detailed voiding history, local examination, uroflowmetry, calibration, and micturating cystourethrogram. Results: All patients had mid-urethral stricture. Mean age was 47.5 years. Mean Q max improved from 6.2 to 27.6 ml/s. Mean residual volume decreased from 160 to 20 ml. Mean duration of follow-up was 24.5 months (6 months to 3 years. Only one patient required self-calibration for 6 months after which her stricture stabilized. None of the patient was incontinent. Conclusion: Dorsal vaginal onlay graft urethroplasty could be considered as an effective way to treat female urethral stricture.

The morphometric analysis of the intervertebral foramen and the spinal nerve root in the cervical spine

International Nuclear Information System (INIS)

Yoshida, Yasuo

2008-01-01

deg at C5 and C6, showing a significantly obtuse angle at C5 and C6 compared with at C3. The measurement at the merging section of the dorsal spinal nerve root showed that the width was about 7.0 to 7.5 mm at C3 through C6 and about 6.5 mm at C7 which was significantly low, while the cephalocaudal length was about 12.5 mm at C3, about 11.5 mm at C4, about 12 to 13 mm at C5, about 11.5 mm at C6, about 10.5 mm at C7, and about 10 mm at C8: there was a difference between the right and the left at C5, whereas no difference was observed between the right and the left at C3, C4, C6, C7, and C8. The incidence angle from the inlet of intervertebral foramen of the dorsal spinal nerve root toward the superior part of the spine indistinct a gradual obtuse angle at C3 through C5, whereas the angle gradually become an acute angle at C6 or below. The incidence angle in the inferior part was obtuse at C4 and C5, and acute at C6 or below, showing that the distance obliquely running within the dura mater tended to be short in the dorsal nerve rootlets at C4 and C5. Based on the above results, it was considered that the anatomy of the intervertebral foramen of the cervical spine and the difference by level at the origin of dorsal root have an influence on the onset of cervical myelopathy and cervical spondylotic radiculopathy as well as the occurrence of various types of disease states. (author)

The functional anatomy of speech perception: Dorsal and ventral processing pathways

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Hickok, Gregory

2003-04-01

Drawing on recent developments in the cortical organization of vision, and on data from a variety of sources, Hickok and Poeppel (2000) have proposed a new model of the functional anatomy of speech perception. The model posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, involved in mapping sound onto meaning, and a dorsal stream, involved in mapping sound onto articulatory-based representations. The ventral stream projects ventrolaterally toward inferior posterior temporal cortex which serves as an interface between sound and meaning. The dorsal stream projects dorsoposteriorly toward the parietal lobe and ultimately to frontal regions. This network provides a mechanism for the development and maintenance of ``parity'' between auditory and motor representations of speech. Although the dorsal stream represents a tight connection between speech perception and speech production, it is not a critical component of the speech perception process under ecologically natural listening conditions. Some degree of bi-directionality in both the dorsal and ventral pathways is also proposed. A variety of recent empirical tests of this model have provided further support for the proposal.

Upregulation of calcium channel alpha-2-delta-1 subunit in dorsal horn contributes to spinal cord injury-induced tactile allodynia.

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Kusuyama, Kazuki; Tachibana, Toshiya; Yamanaka, Hiroki; Okubo, Masamichi; Yoshiya, Shinichi; Noguchi, Koichi

2018-01-31

Spinal cord injury (SCI) commonly results not only in motor paralysis but also in the emergence of neuropathic pain (NeuP), both of which can impair the quality of life for patients with SCI. In the clinical field, it is well known that pregabalin, which binds to the voltage-gated calcium channel alpha-2-delta-1 (α 2 δ-1) subunit has therapeutic effects on NeuP after SCI. A previous study has demonstrated that SCI increased α 2 δ-1 in the L4-L6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase of α 2 δ-1 was correlated with tactile allodynia of the hind paw. However, the detailed feature of an increase in α 2 δ-1 protein in the spinal dorsal horn and the mechanism of pregabalin effect on SCI-induced NeuP have not been fully examined. This study aimed to examine the detailed distribution of α 2 δ-1 expression in the lumbar spinal cord after thoracic SCI in rats and the correlation of the therapeutic effect of pregabalin in SCI rats. Male Sprague-Dawley rats underwent thoracic (T10) spinal cord contusion injury using the IH impactor device. Spinal cord injury rats received pregabalin (30 mg/kg) once a day for 2 weeks over a 4-week period after SCI. The mechanical threshold in the rat hind paw was measured over 4 weeks. Alpha-2-delta-1 expression in the lumbar spinal cord and in the dorsal root ganglion (DRG) was analyzed using immunohistochemistry and in situ hybridization histochemistry. A significant reduction of the withdrawal threshold of mechanical stimuli to the hind paw was observed for 2 weeks and continued at least 4 weeks after SCI. In the control rats, expression of α 2 δ-1 immunoreactivity was detected mainly in laminae I and II in the lumbar dorsal horn. Thoracic SCI significantly increased α 2 δ-1 immunoreactivity in laminae I and II in the lumbar dorsal horn 4 weeks after SCI; however, thoracic SCI did not affect the expression of α 2 δ-1 mRNA in the L4 and L5 DRGs. Meanwhile, the signal intensity of α 2 �

Distribution of binding sites for the plant lectin Ulex europaeus agglutinin I on primary sensory neurones in seven different mammalian species.

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Gerke, Michelle B; Plenderleith, Mark B

2002-01-01

There is an increasing body of evidence to suggest that different functional classes of neurones express characteristic cell-surface carbohydrates. Previous studies have shown that the plant lectin Ulex europaeus agglutinin-I (UEA) binds to a population of small to medium diameter primary sensory neurones in rabbits and humans. This suggests that a fucose-containing glycoconjugate may be expressed by nociceptive primary sensory neurones. In order to determine the extent to which this glycoconjugate is expressed by other species, in the current study, we have examined the distribution of UEA-binding sites on primary sensory neurones in seven different mammals. Binding sites for UEA were associated with the plasma membrane and cytoplasmic granules of small to medium dorsal root ganglion cells and their axon terminals in laminae I-III of the grey matter of the spinal cord, in the rabbit, cat and marmoset monkey. However, no binding was observed in either the dorsal root ganglia or spinal cord in the mouse, rat, guinea pig or flying fox. These results indicate an inter-species variation in the expression of cell-surface glycoconjugates on mammalian primary sensory neurones.

Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks.

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Su-Hyun Kim

Full Text Available Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC and object-location recognition tasks were impaired in recent (1 day memory test while passive avoidance task was impaired only in remote (≥ 20 days memory in KO mice. Results using adeno-associated virus (AAV-mediated Cav1.3 knock-down (KD or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task.

Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks.

Science.gov (United States)

Kim, Su-Hyun; Park, Ye-Ryoung; Lee, Boyoung; Choi, Byungil; Kim, Hyun; Kim, Chong-Hyun

2017-01-01

Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO) of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB) filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC) and object-location recognition tasks were impaired in recent (1 day) memory test while passive avoidance task was impaired only in remote (≥ 20 days) memory in KO mice. Results using adeno-associated virus (AAV)-mediated Cav1.3 knock-down (KD) or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task.

A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

DEFF Research Database (Denmark)

Hoeber, Jan; Konig, Niclas; Trolle, Carl

2017-01-01

Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso...... their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient...

WE-EF-BRA-11: Precision Partial-Tumor Irradiation of Dorsal Rodent Mammary Tumors

Energy Technology Data Exchange (ETDEWEB)

Malcolm, J [Duke Medical Physics Graduate Program, Durham, NC (United States); Boss, K [Department of Comparative Biomedical Sciences, North Carolina State University (United States); Dewhirst, M [Dpt of Radiation and Cancer Biology, Duke University, Durham, North Carolina (United States); Oldham, M [Dpt of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2015-06-15

Purpose: To introduce a pre-clinical treatment technique on a micro-irradiator to treat specific volumes of dorsal mammary tumors in BALB/c mice while sparing lungs and spine. This technique facilitates pre-clinical investigation of tumor response to sub-optimal radiation treatments in which a portion of the tumor is unirradiated, known as a “marginal miss”. In-vitro data suggests that partial tumor radiations trigger a more aggressive phenotype in non-irradiated, regional tumor cells via bystander effects. As the lung tissue is spared, the impact of marginal miss on the development of pulmonary metastasis may be assessed. Methods: End to end test was performed on three BALB/c mice as proof of concept for larger studies. 1Gy was delivered on the micro-irradiator employing previously unexplored lateral parallel-opposed diamond and/or triangle-shaped beams. The margins of the treatment beam were defined using a combination of tumor palpation, barium fiducial markers, and real-time fluoroscopic images. The dose distribution was independently verified with kilovoltage beam Monte Carlo dose calculations with 7% statistical uncertainty and double exposure images. As a final step, the technique was used in a larger pre-clinical study (15Gy, 36 BALB/c mice) and lung metastasis in response to tumor irradiation of 100%, 50% and 0% was quantified. Results: For the Monte-Carlo dose calculations, the dose volume histograms established a maximum dose within the un-irradiated and radiated portions of the mammary tumor of 0.3Gy and 1.5Gy respectively, with a sharp gradient at the boundary. 100% of the lung volume received less than 0.5Gy. This technique proved suitable for a pre-clinical marginal miss study with 50% more lung metastases in partially-radiated mouse models compared to completely. Conclusion: We have developed a novel treatment technique for partial or full irradiation of dorsal mammary tumors incorporating lung sparing.The technique will be useful for exploring

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

International Nuclear Information System (INIS)

Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

2010-01-01

Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

Energy Technology Data Exchange (ETDEWEB)

Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

2010-07-16

Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

Borders and Comparative Cytoarchitecture of the Perirhinal and Postrhinal Cortices in an F1 Hybrid Mouse

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Beaudin, Stephane A.; Singh, Teghpal; Agster, Kara L.

2013-01-01

We examined the cytoarchitectonic and chemoarchitectonic organization of the cortical regions associated with the posterior rhinal fissure in the mouse brain, within the framework of what is known about these regions in the rat. Primary observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1 hybrid was chosen because of the many advantages afforded in the study of the molecular and cellular bases of learning and memory. Comparisons with the parent strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was processed for visualization of Nissl material, myelin, acetyl cholinesterase, parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm’s method was particularly useful in the assignment of borders and in the comparative analyses because the patterns of staining were similar across species and strains. As in the rat, the areas examined were parcellated into 2 regions, the perirhinal and the postrhinal cortices. The perirhinal cortex was divided into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd) and ventral (PORv) subregions. In addition to identifying the borders of the perirhinal cortex, we were able to identify a region in the mouse brain that shares signature features with the rat postrhinal cortex. PMID:22368084

A case of dorsal oblique fingertip amputation.

Science.gov (United States)

Takeda, Shinsuke; Tatebe, Masahiro; Morita, Akimasa; Yoneda, Hidemasa; Iwatsuki, Katsuyuki; Hirata, Hitoshi

2017-01-01

This study reports successful finger replantation in a patient with a dorsal oblique fingertip amputation. When repairing this unique type of injury, an evaluation of the remaining vessels is more useful for successful replantation than the anatomical zone classification. We propose that Kasai's classification is appropriate for guiding treatment.

Dorsal stream involvement in recognition of objects with transient onset but not with ramped onset

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Lourenco Tomas

2011-08-01

Full Text Available Abstract Background Although the ventral visual stream is understood to be responsible for object recognition, it has been proposed that the dorsal stream may contribute to object recognition by rapidly activating parietal attention mechanisms, prior to ventral stream object processing. Methods To investigate the relative contribution of the dorsal visual stream to object recognition a group of tertiary students were divided into good and poor motion coherence groups and assessed on tasks classically assumed to rely on ventral stream processing. Participants were required to identify simple line drawings in two tasks, one where objects were presented abruptly for 50 ms followed by a white-noise mask, the other where contrast was linearly ramped on and off over 325 ms and replaced with a mask. Results Although both groups only differed in motion coherence performance (a dorsal stream measure, the good motion coherence group showed superior contrast sensitivity for object recognition on the abrupt, but not the ramped presentation tasks. Conclusions We propose that abrupt presentation of objects activated attention mechanisms fed by the dorsal stream, whereas the ramped presentation had reduced transience and thus did not activate dorsal attention mechanisms as well. The results suggest that rapid dorsal stream activation may be required to assist with ventral stream object processing.

Diagnosis of dorsal inter osseous pseudotumours by magnetic resonance imaging

International Nuclear Information System (INIS)

Peh, W.C.G.; Wong, L.L.S.; Ip, W.Y.

1999-01-01

Two middle-aged-patients each presenting with a progressively enlarging mass in the first dorsal web space of their hands are reported. Magnetic resonance imaging (MRI) demonstrated the cause to be a hypertrophic first dorsal inter osseous muscle, with normal T1, T2 and post-gadopentetate dimeglumine signal characteristics. The ability of MRI to diagnose anatomical variants of hand muscles is important in the clinical management of patients with these pseudotumours. The usefulness of magnetic resonance imaging (MRI) in evaluation of soft tissue tumours of the musculoskeletal system is now widely accepted. Its ability to maximize contrast between tumour and adjacent normal tissue in a multiplanar manner makes it the imaging modality of choice in pre-operative staging of soft tissue masses. In the hand and wrist, where benign tumours predominate, MRI may provide a specific diagnosis. We describe two cases in which MRI demonstrated the cause of a hand pseudotumour to be due to hypertrophy of the first dorsal inter osseous muscle. Copyright (1999) Blackwell Science Pty Ltd

Diagnosis of dorsal inter osseous pseudotumours by magnetic resonance imaging

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Peh, W.C.G.; Wong, L.L.S. [The University of Hong Kong, Queen Mary Hospital, (Hong Kong). Hand Surgery Division, Department of Diagnotic Radiology; Ip, W.Y. [The University of Hong Kong, Queen Mary Hospital, (Hong Kong). Hand Surgery Division, Department of Orthopaedic Surgery

1999-08-01

Two middle-aged-patients each presenting with a progressively enlarging mass in the first dorsal web space of their hands are reported. Magnetic resonance imaging (MRI) demonstrated the cause to be a hypertrophic first dorsal inter osseous muscle, with normal T1, T2 and post-gadopentetate dimeglumine signal characteristics. The ability of MRI to diagnose anatomical variants of hand muscles is important in the clinical management of patients with these pseudotumours. The usefulness of magnetic resonance imaging (MRI) in evaluation of soft tissue tumours of the musculoskeletal system is now widely accepted. Its ability to maximize contrast between tumour and adjacent normal tissue in a multiplanar manner makes it the imaging modality of choice in pre-operative staging of soft tissue masses. In the hand and wrist, where benign tumours predominate, MRI may provide a specific diagnosis. We describe two cases in which MRI demonstrated the cause of a hand pseudotumour to be due to hypertrophy of the first dorsal inter osseous muscle. Copyright (1999) Blackwell Science Pty Ltd 20 refs., 3 figs.

Pulsed Radiofrequency Applied to the Sciatic Nerve Improves Neuropathic Pain by Down-regulating The Expression of Calcitonin Gene-related Peptide in the Dorsal Root Ganglion

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Ren, Hao; Jin, Hailong; Jia, Zipu; Ji, Nan; Luo, Fang

2018-01-01

Background: Clinical studies have shown that applying pulsed radiofrequency (PRF) to the neural stem could relieve neuropathic pain (NP), albeit through an unclear analgesic mechanism. And animal experiments have indicated that calcitonin gene-related peptide (CGRP) expressed in the dorsal root ganglion (DRG) is involved in generating and maintaining NP. In this case, it is uncertain whether PRF plays an analgesic role by affecting CGRP expression in DRG. Methods: Rats were randomly divided into four groups: Groups A, B, C, and D. In Groups C and D, the right sciatic nerve was ligated to establish the CCI model, while in Groups A and B, the sciatic nerve was isolated without ligation. After 14 days, the right sciatic nerve in Groups B and D re-exposed and was treated with PRF on the ligation site. Thermal withdrawal latency (TWL) and hindpaw withdrawal threshold (HWT) were measured before PRF treatment (Day 0) as well as after 2, 4, 8, and 14 days of treatment. At the same time points of the behavioral tests, the right L4-L6 DRG was sampled and analyzed for CGRP expression using RT-qPCR and an enzyme-linked immunosorbent assay (ELISA). Results: Fourteen days after sciatic nerve ligation, rats in Groups C and D had a shortened TWL (P 0.05). On the 8th and 14th days, the mRNA levels in Group D were restored to those of Groups A and B. Meanwhile, the CGRP content of Group D gradually dropped over time, from 76.4 pg/mg (Day 0) to 57.5 pg/mg (Day 14). Conclusions: In this study, we found that, after sciatic nerve ligation, rats exhibited apparent hyperalgesia and allodynia, and CGRP mRNA and CGRP contents in the L4-L6 DRG increased significantly. Through lowering CGRP expression in the DRG, PRF treatment might relieve the pain behaviors of NP. PMID:29333099

Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

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Ghazizadeh, Vahid; Nazıroğlu, Mustafa

2014-09-01

Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

Persistent dorsal ophthalmic artery arising from the internal carotid artery: Report of three cases

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Shin, Jae Hwan; Lee, Ghi Jai; Shim, Jae Chan; Lee, Kyoung Eun; Kim, Ho Kyun; Suh, Jung Ho [Dept. of Radiology, Seoul Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

2016-12-15

Normally, the ophthalmic artery (OA) arises from the supraclinoid segment of the internal carotid artery (ICA) and enters the orbit via the optic canal. A persistent dorsal OA is a rare variation that originates from the cavernous segment of the ICA and enters the orbit via the superior orbital fissure. To the best of our knowledge, persistent dorsal OA has not been described in the Korean literature. In this paper, we report three cases of persistent dorsal OA with review of the literature on embryogenesis and other origins of the OA.

Dorsal onlay graft bulbar urethroplasty using buccal mucosa

African Journals Online (AJOL)

G. Barbagli

2015-12-02

Dec 2, 2015 ... promote the transformation of the urethral mucosa plate into a tube, according to ... Allen stirrups and sequential inflatable compression sleeves. Figure 2 .... the ventral, dorsal or lateral surface of the urethra, we investigated if.

Investigating category- and shape-selective neural processing in ventral and dorsal visual stream under interocular suppression.

Science.gov (United States)

Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido

2015-01-01

Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

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Laura A. Runck

2014-04-01

Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

A case of dorsal oblique fingertip amputation

OpenAIRE

Takeda, Shinsuke; Tatebe, Masahiro; Morita, Akimasa; Yoneda, Hidemasa; Iwatsuki, Katsuyuki; Hirata, Hitoshi

2017-01-01

Abstract This study reports successful finger replantation in a patient with a dorsal oblique fingertip amputation. When repairing this unique type of injury, an evaluation of the remaining vessels is more useful for successful replantation than the anatomical zone classification. We propose that Kasai?s classification is appropriate for guiding treatment.

Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell.

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Julie Dufour

Full Text Available Recent studies underline the implication of Liver X Receptors (LXRs in several prostate diseases such as benign prostatic hyperplasia (BPH and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs of wild type (WT or Lxrαβ-/- mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxrαβ-/- mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer.

Bulbar urethroplasty using the dorsal approach: current techniques

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Barbagli Guido

2003-01-01

Full Text Available INTRODUCTION: The use of flaps or grafts is mandatory in patients with longer and complex strictures. In 1995-96 we described a new dorsal onlay graft urethroplasty. Over time, our original technique was better defined and changed. Now this procedure (also named Barbagli technique has been greeted with a fair amount of enthusiasm in Europe and in the United States. SURGICAL TECHNIQUE: The patient is placed in normal lithotomy position, and a midline perineo-scrotal incision is made. The bulbar urethra is then free from the bulbo-cavernous muscles, and is dissected from the corpora cavernosa. The urethra is completely mobilized from the corpora cavernosa, it is rotated 180 degrees, and is incised along its dorsal surface. The graft (preputial skin or buccal mucosa or the flap is fixed and quilted to the tunica albuginea of the corporal bodies. The right mucosal margin of the opened urethra is sutured to the right side of the patch-graft. The urethra is rotated back into its original position. The left urethral margin is sutured to the left side of the patch graft and to the corporal bodies, and the grafted area is entirely covered by the urethral plate. The bulbo-cavernous muscles are approximated over the grafted area. A 16F silicone Foley catheter is left in place. COMMENTS: Dorsal onlay graft urethroplasty is a versatile procedure that may be combined with various substitute materials like preputial skin, buccal mucosa grafts or pedicled flaps.

Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 regulates axon integrity in the mouse embryo.

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Amy N Hicks

Full Text Available Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder. Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2. Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2(blad/blad mutants. Examination of the brains of E18.5 Nmnat2(blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2(blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG. In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

Proximally evoked soleus H-reflex to S1 nerve root stimulation in sensory neuronopathies (ganglionopathies).

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Zhu, Dong-Qing; Zhu, Yu; Qiao, Kai; Zheng, Chao-Jun; Bradley, Scott; Weber, Robert; Chen, Xiang-Jun

2013-11-01

Sensory neuronopathy (SNN) mimics distal sensory axonopathy. The conventional H-reflex elicited by tibial nerve stimulation (tibial H-reflex) is usually abnormal in both conditions. We evaluated the proximally evoked soleus H-reflex in response to S1 nerve root stimulation (S1 foramen H-reflex) in SNN. Eleven patients with SNN and 6 with distal sensory axonopathy were studied. Tibial and S1 foramen H-reflexes were performed bilaterally in each patient. Tibial and S1 foramen H-reflexes were absent bilaterally in all patients with SNN. In the patients with distal sensory axonopathy, tibial H-reflexes were absent in 4 and demonstrated prolonged latencies in 2, but S1 foramen H-reflexes were normal. Characteristic absence of the H-reflex after both proximal and distal stimulation reflects primary loss of dorsal root ganglion (DRG) neurons and the distinct non-length-dependent impairment of sensory nerve fibers in SNN. Copyright © 2013 Wiley Periodicals, Inc.

Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon.

Science.gov (United States)

Stenman, Jan; Yu, Ruth T; Evans, Ronald M; Campbell, Kenneth

2003-03-01

We have examined the role of Tlx, an orphan nuclear receptor, in dorsal-ventral patterning of the mouse telencephalon. Tlx is expressed broadly in the ventricular zone, with the exception of the dorsomedial and ventromedial regions. The expression spans the pallio-subpallial boundary, which separates the dorsal (i.e. pallium) and ventral (i.e. subpallium) telencephalon. Despite being expressed on both sides of the pallio-subpallial boundary, Tlx homozygous mutants display alterations in the development of this boundary. These alterations include a dorsal shift in the expression limits of certain genes that abut at the pallio-subpallial boundary as well as the abnormal formation of the radial glial palisade that normally marks this boundary. The Tlx mutant phenotype is similar to, but less severe than, that seen in Small eye (i.e. Pax6) mutants. Interestingly, removal of one allele of Pax6 on the homozygous Tlx mutant background significantly worsens the phenotype. Thus Tlx and Pax6 cooperate genetically to regulate the establishment of the pallio-subpallial boundary. The patterning defects in the Tlx mutant telencephalon result in a loss of region-specific gene expression in the ventral-most pallial region. This correlates well with the malformation of the lateral and basolateral amygdala in Tlx mutants, both of which have been suggested to derive from ventral portions of the pallium.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

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Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

2018-01-01

Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a

OpenAIRE

Deuis, J. R.; Dekan, Z.; Wingerd, J. S.; Smith, J. J.; Munasinghe, N. R.; Bhola, R. F.; Imlach, W. L.; Herzig, V.; Armstrong, D. A.; Rosengren, K. J.; Bosmans, F.; Waxman, S. G.; Dib-Hajj, S. D.; Escoubas, P.; Minett, M. S.

2017-01-01

Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed...

A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.

Science.gov (United States)

Cardoso, Maira Arruda; Fontenele, Marcio; Lim, Bomyi; Bisch, Paulo Mascarello; Shvartsman, Stanislav Y; Araujo, Helena Marcolla

2017-08-15

The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals. © 2017. Published by The Company of Biologists Ltd.

Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

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Sadhu Rejina

2007-12-01

Full Text Available Abstract Background During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS and the central nervous system (CNS. Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS. Results Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point. Conclusion Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

Anatomy and muscle activity of the dorsal fins in bamboo sharks and spiny dogfish during turning maneuvers.

Science.gov (United States)

Maia, Anabela; Wilga, Cheryl D

2013-11-01

Stability and procured instability characterize two opposing types of swimming, steady and maneuvering, respectively. Fins can be used to manipulate flow to adjust stability during swimming maneuvers either actively using muscle control or passively by structural control. The function of the dorsal fins during turning maneuvering in two shark species with different swimming modes is investigated here using musculoskeletal anatomy and muscle function. White-spotted bamboo sharks are a benthic species that inhabits complex reef habitats and thus have high requirements for maneuverability. Spiny dogfish occupy a variety of coastal and continental shelf habitats and spend relatively more time cruising in open water. These species differ in dorsal fin morphology and fin position along the body. Bamboo sharks have a larger second dorsal fin area and proportionally more muscle insertion into both dorsal fins. The basal and radial pterygiophores are plate-like structures in spiny dogfish and are nearly indistinguishable from one another. In contrast, bamboo sharks lack basal pterygiophores, while the radial pterygiophores form two rows of elongated rectangular elements that articulate with one another. The dorsal fin muscles are composed of a large muscle mass that extends over the ceratotrichia overlying the radials in spiny dogfish. However, in bamboo sharks, the muscle mass is divided into multiple distinct muscles that insert onto the ceratotrichia. During turning maneuvers, the dorsal fin muscles are active in both species with no differences in onset between fin sides. Spiny dogfish have longer burst durations on the outer fin side, which is consistent with opposing resistance to the medium. In bamboo sharks, bilateral activation of the dorsal in muscles could also be stiffening the fin throughout the turn. Thus, dogfish sharks passively stiffen the dorsal fin structurally and functionally, while bamboo sharks have more flexible dorsal fins, which result from a

Posture And Dorsal Shape At A Sitted Workstation

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Lepoutre, F. X.; Cloup, P.; Guerra, T. M.

1986-07-01

The ergonomic analysis of a control or a supervision workstation for a vehicle or a process, necessitates to take into account the biomecanical visuo-postural system. The measurements, which are necessary to do, must give informations about the spatial direction of the limbs, the dorsal shape, eventually the eyes direction, and the postural evolution during the working time. More, the smallness of the work station, the backrest and sometime a vibratory environment made use specific, strong and small devices wich do not disturb the operator. The measurement system which we propose is made of an optical device. This system is studied in relation with the french "Institute de Recherche pour les Transports" for an ergonomic analysis of a truck cabin. The optical device consists on placing on the body of the driver on particular places materializing specially members and trunck joint points, some drops which reflect the infra-red raies coming from a specific light. Several cameras whose relative positions depend on the experiment site, transmit video signals to the associated treatment systems which extract the coordinates (Xi, Yi) of each drop in the observation scope of any camera. By regrouping the informations obtained from every view, it is possible to obtain the spatial drop position and then to restore the individual's posture in three dimensions. Therefore, this device doesn't enable us, in consideration of the backrest, to analyse the dorsal posture, which is important with regard to dorsal pains frequency. For that reason, we complete the measurements by using a "curvometer". This device consists of a flexible stick fixed upon the individual back with elastic belts, whose distorsions (curvature in m-1) are measured, in the individual's sagittal plane, with 4 strain gauges pairs; located approximately at the level of vertebra D1, D6, D10 and L3. A fifth measurement, concerning the inclination (in degree) of the lower part of the stick, makes it is possible to

Dorsal Branches of Abdominal Aorta in the Rabbit and the European Hare

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Flešárová S.

2016-06-01

Full Text Available The aim of this study was to describe the anatomical arrangement of the branches arising from the dorsal surface of the aorta abdominalis in the rabbit and the hare. The study was carried out on ten adult rabbits and ten adult European hares using the corrosion technique. After the euthanasia, the vascular network was perfused with saline. After polymerization of the casting medium, the maceration was carried out in a KOH solution. We found different variations in; the number of arteries, level of their origin and arrangement. The aa. lumbales of the same level arose by means of a common trunk or their origin was independent. The aa. lumbales VI or aa. lumbales VI et VII originated also from the a. sacralis mediana. By aa. lumbales we found an important interspecies difference in; number, diameter, ramification and density of dorsal branches, which are designated for the dorsal muscles of the body stem. All listed parameters of branches were higher in the hare. This anatomical arrangement of dorsal branches is adapted to the higher movement activity of the hare. According to our results, it can be concluded that the anatomical arrangement of the branches of the aorta abdominalis shows a higher number of variations in the domesticated rabbit in comparison with the hare.

Dorsal free graft urethroplasty for urethral stricture by ventral sagittal urethrotomy approach.

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Asopa, H S; Garg, M; Singhal, G G; Singh, L; Asopa, J; Nischal, A

2001-11-01

To explore the feasibility of applying a dorsal free graft to treat urethral stricture by the ventral sagittal urethrotomy approach without mobilizing the urethra. Twelve patients with long or multiple strictures of the anterior urethra were treated by a dorsal free full-thickness preputial or buccal mucosa graft. The urethra was not separated from the corporal bodies and was opened in the midline over the stricture. The floor of the urethra was incised, and an elliptical raw area was created over the tunica on which a free full-thickness graft of preputial or buccal mucosa was secured. The urethra was retubularized in one stage. After a follow-up of 8 to 40 months, one recurrence developed and required dilation. The ventral sagittal urethrotomy approach for dorsal free graft urethroplasty is not only feasible and successful, but is easy to perform.

Dorsal onlay lingual mucosal graft urethroplasty for urethral strictures in women.

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Sharma, Girish K; Pandey, Ashwani; Bansal, Harbans; Swain, Sameer; Das, Suren K; Trivedi, Sameer; Dwivedi, Udai S; Singh, Pratap B

2010-05-01

To describe the technique and results of dorsal onlay lingual mucosal graft (LMG) urethroplasty for the definitive management of urethral strictures in women. In all, 15 women (mean age 42 years) with a history suggestive of urethral stricture who had undergone multiple urethral dilatations and/or urethrotomy were selected for dorsal onlay LMG urethroplasty after thorough evaluation, from October 2006 to March 2008. After a suprameatal inverted-U incision, the dorsal aspect of the urethra was dissected and urethrotomy was done at the 12 o'clock position across the strictured segment. Tailored LMG harvested from the ventrolateral aspect of the tongue was then sutured to the urethrotomy wound over an 18 F silicone catheter. The preoperative mean maximum urinary flow rate of 7.2 mL/s increased to 29.87 mL/s, 26.95 mL/s and 26.86 mL/s with a 'normal' flow rate curve at 3, 6 and 12 months follow-up, respectively. One patient at the 3-month follow-up had submeatal stenosis and required urethral dilatation thrice at monthly intervals. At the 1-year follow-up, none of the present patients had any neurosensory complications, urinary incontinence, or long-term functional/aesthetic complication at the donor site. LMG urethroplasty using the dorsal onlay technique should be offered for correction of persistent female urethral stricture as it provides a simple, safe and effective approach with durable results.

Shape representations in the primate dorsal visual stream

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Tom eTheys

2015-04-01

Full Text Available The primate visual system extracts object shape information for object recognition in the ventral visual stream. Recent research has demonstrated that object shape is also processed in the dorsal visual stream, which is specialized for spatial vision and the planning of actions. A number of studies have investigated the coding of 2D shape in the anterior intraparietal area (AIP, one of the end-stage areas of the dorsal stream which has been implicated in the extraction of affordances for the purpose of grasping. These findings challenge the current understanding of area AIP as a critical stage in the dorsal stream for the extraction of object affordances. The representation of three-dimensional (3D shape has been studied in two interconnected areas known to be critical for object grasping: area AIP and area F5a in the ventral premotor cortex (PMv, to which AIP projects. In both areas neurons respond selectively to 3D shape defined by binocular disparity, but the latency of the neural selectivity is approximately 10 ms longer in F5a compared to AIP, consistent with its higher position in the hierarchy of cortical areas. Furthermore F5a neurons were more sensitive to small amplitudes of 3D curvature and could detect subtle differences in 3D structure more reliably than AIP neurons. In both areas, 3D-shape selective neurons were co-localized with neurons showing motor-related activity during object grasping in the dark, indicating a close convergence of visual and motor information on the same clusters of neurons.

Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

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Bonino, D; Ricciardi, E; Sani, L; Gentili, C; Vanello, N; Guazzelli, M; Vecchi, T; Pietrini, P

2008-09-01

In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

Right dorsal colon ultrasonography in normal adult ponies and miniature horses

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Zak, Agnieszka; Baron, Monika; Cylna, Marta; Borowicz, Hieronim

2017-01-01

The aim of this study was to determine the normal location, wall thickness and motility of the right dorsal colon in adult ponies and miniature horses. The abdominal ultrasonography examination was performed in a study group consisting of 23 ponies and miniature horses and in a control group comprising ten Thoroughbred horses. The procedure was performed in unsedated standing animals. The location and the thickness of the right dorsal colonic wall was examined on the right side of the abdomen between the 10th and the 14th intercostal space. The contractility was recorded in the 12th intercostal space. A comparative analysis between the study group and control group was carried out using the Student’s t-test. Pearson’s linear correlation coefficient was used to calculate the correlation between the thickness of the colonic wall as well as the number of peristaltic movements and age, wither height and body mass of the animals. The right dorsal colon was identified in all the horses in the 12th intercostal space. In all the intercostal spaces the mean ± standard deviation (SD) wall thickness of the right dorsal colon was 0.27 ± 0.03 cm in the horses from the study group and 0.37 ± 0.03 cm in the control horses. The mean number of peristaltic contractions was 4.05 ± 1.07 per minute in the animals from the study group and 1.7 ± 0.46 contractions per minute in the control group. The values of the ultrasonographic wall thickness and peristaltic motility in small breed horses in the present study were different from the values obtained for large breed horses. The study also found that the right dorsal colon in small breed horses is physiologically located in the 12th intercostal space. This suggests that different reference values should be used in small horse breeds when performing an ultrasound examination. PMID:29065146

Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats

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Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

2013-01-01

The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

Rare patterns of dorsal puncture in Pterostichus oblongopunctatus (Coleoptera: Carabidae

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Axel Schwerk

2018-04-01

Full Text Available Background The carabid beetle species Pterostichus oblongopunctatus is common in different types of forests in Poland and Europe. With respect to this species, some unclarities exist concerning the morphological feature of punctures on the elytra. P. oblongopunctatus has dorsal pits in the third interval of the elytra, the available identification keys, however, provide inconsistent information concerning the puncture in other intervals. During long-term studies at different study sites in Poland, the first author rarely but regularly discovered individuals with unusual dorsal puncture patterns, i.e., pits in the fifth and even in the seventh interval of the elytra. Since such rare patterns might be connected with special habitat characteristics, and thus have a potential as an indicator, the aim of the study was to test if they are connected with specific subpopulations (interaction groups, if they are related to the sex or size of the beetles, and if they are related to specific habitat conditions. Material and Methods We counted the pits on the elytra, determined the sex, and measured the length of the right elytron of individuals of P. oblongopunctatus collected at numerous study sites located within the borders of the Regional Directory of National Forests in Piła (Western Poland over the period 2014–2016. Results Altogether, 1,058 individuals of P. oblongopunctatus were subjected to statistical analysis. Almost 19% of the individuals had a dorsal puncture in the fifth interval of the elytra and about 0.7% had a dorsal puncture in the seventh interval of the elytra. In 2014 and 2015, significantly more females exhibited such unusual patterns of dorsal puncture than males. Even if not statistically significant, in 2016 also relatively more females showed such a pattern. Neither males nor females of the analysed individuals with usual puncture patterns showed a significant difference in the length of the right elytron from those with

The ventral stream offers more affordance and the dorsal stream more memory than believed

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Postma, Albert; van der Lubbe, Robert Henricus Johannes; Zuidhoek, Sander

2002-01-01

Opposed to Norman's proposal, processing of affordance is likely to occur not solely in the dorsal stream but also in the ventral stream. Moreover, the dorsal stream might do more than just serve an important role in motor actions. It supports egocentric location coding as well. As such, it would

RESULTS OF DIAGNOSTICAL BLOCK OF LONG DORSAL SACROILIAC LIGAMENT UNDER SONOGRAPHIC CONTROL IN PATIENTS WITH LOW BACK PAIN

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Yurkovskiy A. M.

2018-02-01

Full Text Available Purpose: to improve effectiveness of diagnostic block of long dorsal sacroiliac ligament performed under sonographic control in patients with low back pain caused by pathology of this ligament. Material and methods: the research included 35 patients (average age 46,2±12,5 years with symptoms of low back pain caused by pathology of long dorsal sacroiliac ligament. Diagnostical block of the given ligament was made under ultrasound control. Results: significant pain syndrome reduction was observed in all patients with ligamentopathy of long dorsal sacroiliac ligament. Conclusion: compared to "blind" technique, long dorsal sacroiliac ligament block performed under sonographic control is a more efficient method of verification and treatment for low back pain syndrome in case of long dorsal sacroiliac ligament injury.

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

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Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

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Daniel P Holschneider

2014-06-01

Full Text Available Rodent cortical midline structures (CMS are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas--findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways will not only critically inform future work at the microscopic (single neurons and synapses level, but also have translational value to advance our understanding of human brain

Accelerated forgetting of contextual details due to focal medio-dorsal thalamic lesion

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Sicong eTu

2014-09-01

Full Text Available Effects of thalamic nuclei damage and related white matter tracts on memory performance are still debated. This is particularly evident for the medio-dorsal thalamus which has been less clear in predicting amnesia than anterior thalamus changes. The current study addresses this issue by assessing 7 thalamic stroke patients with consistent unilateral lesions focal to the left medio-dorsal nuclei for immediate and delayed memory performance on standard visual and verbal tests of anterograde memory, and over the long-term (> 24 hrs on an object-location associative memory task. Thalamic patients showed selective impairment to delayed recall, but intact recognition memory. Patients also showed accelerated forgetting of contextual information after a 24 hour delay, compared to controls. Importantly, the mammillothalamic tract was intact in all patients, which suggests a role for the medio-dorsal nuclei in recall and early consolidation memory processes.

S113R mutation in SLC33A1 leads to neurodegeneration and augmented BMP signaling in a mouse model

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Pingting Liu

2017-01-01

Full Text Available The S113R mutation (c.339T>G (MIM #603690.0001 in SLC33A1 (MIM #603690, an ER membrane acetyl-CoA transporter, has been previously identified in individuals with hereditary spastic paraplegia type 42 (SPG42; MIM #612539. SLC33A1 has also been shown to inhibit the bone morphogenetic protein (BMP signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1S113R knock-in mice. Homozygous Slc33a1S113R mutant mice were embryonic lethal, whereas heterozygous Slc33a1 mutant mice (Slc33a1wt/mut exhibited behavioral abnormalities and central neurodegeneration, which is consistent with hereditary spastic paraplegia (HSP phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous system and mouse embryonic fibroblasts of Slc33a1wt/mut mice. Using a sciatic nerve crush injury model in vivo and dorsal root ganglion (DRG culture in vitro we showed that injury-induced axonal regeneration in Slc33a1wt/mut mice was accelerated and mediated by upregulated BMP signaling. Exogenous addition of BMP signaling antagonist, noggin, could efficiently alleviate the accelerated injury-induced axonal regrowth. These results indicate that SLC33A1 can negatively regulate BMP signaling in mice, further supporting the notion that upregulation of BMP signaling is a common mechanism of a subset of hereditary spastic paraplegias.

The function of the long dorsal sacroiliac ligament : its implications for understanding low back pain

NARCIS (Netherlands)

Pool-Goudzwaard, A.L.; Vleeming, A; Hammudoghlu, D; Stoeckart, R.; Snijders, C.; Mens, Jan M A

1996-01-01

STUDY DESIGN: In embalmed human bodies the tension of the long dorsal sacroiliac ligament was measured during incremental loading of anatomical structures that are biomechanically relevant. OBJECTIVES: To assess the function of the long dorsal sacroiliac ligament. SUMMARY OF BACKGROUND DATA: In many

Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus.

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Alison P Lee

Full Text Available The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG, recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers.

Dorsal inlay buccal mucosal graft (Asopa) urethroplasty for anterior urethral stricture.

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Marshall, Stephen D; Raup, Valary T; Brandes, Steven B

2015-02-01

Asopa described the inlay of a graft into Snodgrass's longitudinal urethral plate incision using a ventral sagittal urethrotomy approach in 2001. He claimed that this technique was easier to perform and led to less tissue ischemia due to no need for mobilization of the urethra. This approach has subsequently been popularized among reconstructive urologists as the dorsal inlay urethroplasty or Asopa technique. Depending on the location of the stricture, either a subcoronal circumferential incision is made for penile strictures, or a midline perineal incision is made for bulbar strictures. Other approaches for penile urethral strictures include the non-circumferential penile incisional approach and a penoscrotal approach. We generally prefer the circumferential degloving approach for penile urethral strictures. The penis is de-gloved and the urethra is split ventrally to exposure the stricture. It is then deepened to include the full thickness of the dorsal urethra. The dorsal surface is made raw and grafts are fixed on the urethral surface. Quilting sutures are placed to further anchor the graft. A Foley catheter is placed and the urethra is retubularized in two layers with special attention to the staggering of suture lines. The skin incision is then closed in layers. We have found that it is best to perform an Asopa urethroplasty when the urethral plate is ≥1 cm in width. The key to when to use the dorsal inlay technique all depends on the width of the urethral plate once the urethrotomy is performed, stricture etiology, and stricture location (penile vs. bulb).

Osteology of the dorsal vertebrae of the giant titanosaurian sauropod dinosaur Dreadnoughtus schrani from the Late Cretaceous of Argentina

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Kristyn K. Voegele

2017-11-01

Full Text Available Many titanosaurian dinosaurs are known only from fragmentary remains, making comparisons between taxa difficult because they often lack overlapping skeletal elements. This problem is particularly pronounced for the exceptionally large-bodied members of this sauropod clade. Dreadnoughtus schrani is a well-preserved giant titanosaurian from the Upper Cretaceous (Campanian–Maastrichtian Cerro Fortaleza Formation of southern Patagonia, Argentina. Numerous skeletal elements are known for Dreadnoughtus, including seven nearly complete dorsal vertebrae and a partial dorsal neural arch that collectively represent most of the dorsal sequence. Here we build on our previous preliminary description of these skeletal elements by providing a detailed assessment of their serial positional assignments, as well as comparisons of the dorsal vertebrae of Dreadnoughtus with those of other exceptionally large-bodied titanosaurians. Although the dorsal elements of Dreadnoughtus probably belong to two individuals, they exhibit substantial morphological variation that suggests that there is minimal, if any, positional overlap among them. Dreadnoughtus therefore preserves the second-most complete dorsal vertebral series known for a giant titanosaurian that has been described in detail, behind only that of Futalognkosaurus. The dorsal sequence of Dreadnoughtus provides valuable insight into serial variation along the vertebral column of these enormous sauropods. Such variation includes the variable presence of divided spinodiapophyseal laminae and associated spinodiapophyseal fossae. Given that dorsal vertebrae are the only elements that overlap between known remains of most giant titanosaurian taxa, the dorsal series of Dreadnoughtus provides a means to directly compare the morphologies of these sauropods. The dorsal vertebrae of Dreadnoughtus and Futalognkosaurus have dorsoventrally narrow transverse processes, unlike the condition in Puertasaurus. Further

Deletion of ENTPD3 does not impair nucleotide hydrolysis in primary somatosensory neurons or spinal cord [v1; ref status: indexed, http://f1000r.es/3rm

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Eric McCoy

2014-07-01

Full Text Available Ectonucleotidases are membrane-bound or secreted proteins that hydrolyze extracellular nucleotides.  Recently, we identified three ectonucleotidases that hydrolyze extracellular adenosine 5’-monophosphate (AMP to adenosine in primary somatosensory neurons.  Currently, it is unclear which ectonucleotidases hydrolyze ATP and ADP in these neurons.  Ectonucleoside triphosphate diphosphohydrolases (ENTPDs comprise a class of enzymes that dephosphorylate extracellular ATP and ADP.  Here, we found that ENTPD3 (also known as NTPDase3 or CD39L3 was located in nociceptive and non-nociceptive neurons of the dorsal root ganglion (DRG, in the dorsal horn of the spinal cord, and in free nerve endings in the skin.  To determine if ENTPD3 contributes directly to ATP and ADP hydrolysis in these tissues, we generated and characterized an Entpd3 knockout mouse.  This mouse lacks ENTPD3 protein in all tissues examined, including the DRG, spinal cord, skin, and bladder.  However, DRG and spinal cord tissues from Entpd3-/- mice showed no reduction in histochemical staining when ATP, ADP, AMP, or UTP were used as substrates.  Additionally, using fast-scan cyclic voltammetry (FSCV, adenosine production was not impaired in the dorsal spinal cord of Entpd3-/- mice when the substrate ADP was applied.  Further, Entpd3-/- mice did not differ in nociceptive behaviors when compared to wild-type mice, although Entpd3-/- mice showed a modest reduction in β-alanine-mediated itch.  Taken together, our data indicate that deletion of Entpd3 does not impair ATP or ADP hydrolysis in primary somatosensory neurons or in dorsal spinal cord.  Moreover, our data suggest there could be multiple ectonucleotidases that act redundantly to hydrolyze nucleotides in these regions of the nervous system.

Deletion of ENTPD3 does not impair nucleotide hydrolysis in primary somatosensory neurons or spinal cord [v2; ref status: indexed, http://f1000r.es/4dl

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Eric McCoy

2014-09-01

Full Text Available Ectonucleotidases are membrane-bound or secreted proteins that hydrolyze extracellular nucleotides.  Recently, we identified three ectonucleotidases that hydrolyze extracellular adenosine 5’-monophosphate (AMP to adenosine in primary somatosensory neurons.  Currently, it is unclear which ectonucleotidases hydrolyze ATP and ADP in these neurons.  Ectonucleoside triphosphate diphosphohydrolases (ENTPDs comprise a class of enzymes that dephosphorylate extracellular ATP and ADP.  Here, we found that ENTPD3 (also known as NTPDase3 or CD39L3 was located in nociceptive and non-nociceptive neurons of the dorsal root ganglion (DRG, in the dorsal horn of the spinal cord, and in free nerve endings in the skin.  To determine if ENTPD3 contributes directly to ATP and ADP hydrolysis in these tissues, we generated and characterized an Entpd3 knockout mouse.  This mouse lacks ENTPD3 protein in all tissues examined, including the DRG, spinal cord, skin, and bladder.  However, DRG and spinal cord tissues from Entpd3-/- mice showed no reduction in histochemical staining when ATP, ADP, AMP, or UTP were used as substrates.  Additionally, using fast-scan cyclic voltammetry (FSCV, adenosine production was not impaired in the dorsal spinal cord of Entpd3-/- mice when the substrate ADP was applied.  Further, Entpd3-/- mice did not differ in nociceptive behaviors when compared to wild-type mice, although Entpd3-/- mice showed a modest reduction in β-alanine-mediated itch.  Taken together, our data indicate that deletion of Entpd3 does not impair ATP or ADP hydrolysis in primary somatosensory neurons or in dorsal spinal cord.  Moreover, our data suggest there could be multiple ectonucleotidases that act redundantly to hydrolyze nucleotides in these regions of the nervous system.

Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK

DEFF Research Database (Denmark)

Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik

2016-01-01

, the presence of PER1 in hippocampal neurons is a prerequisite for the time-of-day-dependent phosphorylation of CREB, as it regulates the shuttling of pP90RSK into the nucleus. Representative immunofluorescence images show a temporal difference in phosphorylated cAMP response element-binding protein (p...... activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility......CREB; green color) levels in all regions of the dorsal hippocampus between a wild-type C3H mouse (WT; left) and a Period1-knockout (Per1−/−; right) mouse. Images were taken 2 h after lights on, thus, when fluctuating levels of pCREB peak in WT mouse hippocampus. Insets show a representative hippocampal neuron...

Demonstration of the dorsal pancreatic artery by CTA to facilitate superselective arterial infusion of stem cells into the pancreas

International Nuclear Information System (INIS)

Lin Yuning; Yang Xizhang; Chen Ziqian; Tan Jianming; Zhong Qun; Yang Li; Wu Zhixian

2012-01-01

Purpose: To investigate the diagnostic performance of 64-section CTA in the detection of dorsal pancreatic artery before interventional therapy for patients with diabetes. Materials and methods: The study was approved by the institutional ethics committee; written informed consent was obtained. Forty-two consecutive patients with diabetes received an experimental treatment of autologous bone marrow-derived stem cell transplantation by means of infusion into the dorsal pancreatic artery. All cases underwent abdominal CTA before angiography of pancreatic arteries in order to locate the origin and course of dorsal pancreatic artery. Angiography of coeliac artery, splenic artery, common hepatic artery and superior mesenteric artery were performed both in CTA and DSA. Superselective catheterization of dorsal pancreatic artery was carried out for the infusion of stem cell. Sensitivity, specificity and accuracy for the detection of dorsal pancreatic artery with CTA were calculated using DSA images as the reference standard. Results: Thirty-five and thirty-six dorsal pancreatic arteries were detected by CTA and DSA respectively. Dorsal pancreatic artery was not visualized in either CTA or DSA in 5 patients. The sensitivity, specificity and accuracy for CTA were 94.4%, 83.3% and 92.9%. Conclusion: 64-section CTA is accurate for the detection of dorsal pancreatic artery. It may be useful for the facilitation of superselective arterial infusion of stem cells to pancreas.

Motor deficits following dorsal corticospinal tract transection in rats: voluntary versus skilled locomotion readouts

Directory of Open Access Journals (Sweden)

Lara Bieler

2018-02-01

The functional relevance of the dorsal CST in locomotion of rats is not as prominent as compared to in humans and thus challenging the motor execution is mandatory to reliably investigate CST function. A detailed analysis of voluntary walking using the CatWalk XT is not adequate to detect deficits following dorsal CST lesion in rats.

Harmane inhibits serotonergic dorsal raphe neurons in the rat.

Science.gov (United States)

Touiki, Khalid; Rat, Pascal; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

2005-11-01

Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively. To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested. In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat. Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane. Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.

Alzheimer disease: functional abnormalities in the dorsal visual pathway.

LENUS (Irish Health Repository)

Bokde, Arun L W

2012-02-01

PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

Dorsal hand coverage with free serratus fascia flap

DEFF Research Database (Denmark)

Fotopoulos, Peter; Holmer, Per; Leicht, Pernille

2003-01-01

in the flap, leaving the long thoracic nerve intact on the serratus muscle. Coverage of the flap with split-thickness skin graft is done immediately. The free serratus fascia flap is an ideal flap for dorsal hand coverage when the extensor tendons are exposed, especially because of low donor-site morbidity....

Genetic association among root morphology, root quality and root yield in ashwagandha (Withania somnifera)

OpenAIRE

Kumar Ramesh R.; Reddy Anjaneya Prasanna L.; Subbaiah Chinna J.; Kumar Niranjana A.; Prasad Nagendra H.N.; Bhukya Balakishan

2011-01-01

Ashwagandha (Withania somnifera) is a dryland medicinal crop and roots are used as valuable drug in traditional systems of medicine. Morphological variants (morphotypes) and the parental populations were evaluated for root - morphometric, quality and yield traits to study genetic association among them. Root morphometric traits (root length, root diameter, number of secondary roots/ plant) and crude fiber content exhibited strong association among them and ...

Neuroimaging investigations of dorsal stream processing and effects of stimulus synchrony in schizophrenia.

Science.gov (United States)

Sanfratello, Lori; Aine, Cheryl; Stephen, Julia

2018-05-25

Impairments in auditory and visual processing are common in schizophrenia (SP). In the unisensory realm visual deficits are primarily noted for the dorsal visual stream. In addition, insensitivity to timing offsets between stimuli are widely reported for SP. The aim of the present study was to test at the physiological level differences in dorsal/ventral stream visual processing and timing sensitivity between SP and healthy controls (HC) using MEG and a simple auditory/visual task utilizing a variety of multisensory conditions. The paradigm included all combinations of synchronous/asynchronous and central/peripheral stimuli, yielding 4 task conditions. Both HC and SP groups showed activation in parietal areas (dorsal visual stream) during all multisensory conditions, with parietal areas showing decreased activation for SP relative to HC, and a significantly delayed peak of activation for SP in intraparietal sulcus (IPS). We also observed a differential effect of stimulus synchrony on HC and SP parietal response. Furthermore, a (negative) correlation was found between SP positive symptoms and activity in IPS. Taken together, our results provide evidence of impairment of the dorsal visual stream in SP during a multisensory task, along with an altered response to timing offsets between presented multisensory stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

Bilateral downregulation of Nav1.8 in dorsal root ganglia of rats with bone cancer pain induced by inoculation with Walker 256 breast tumor cells

International Nuclear Information System (INIS)

Miao, Xue-Rong; Gao, Xiao-Fei; Wu, Jing-Xiang; Lu, Zhi-Jie; Huang, Zhang-Xiang; Li, Xiao-Qing; He, Cheng; Yu, Wei-Feng

2010-01-01

Rapid and effective treatment of cancer-induced bone pain remains a clinical challenge and patients with bone metastasis are more likely to experience severe pain. The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8. Adult female Wistar rats were used for the study. Cancer pain was induced by inoculation of Walker 256 breast carcinosarcoma cells into the tibia. After surgery, mechanical and thermal hyperalgesia and ambulation scores were evaluated to identify pain-related behavior. We used real-time RT-PCR to determine Nav1.8 mRNA expression in bilateral L4/L5 dorsal root ganglia (DRG) at 16-19 days after surgery. Western blotting and immunofluorescence were used to compare the expression and distribution of Nav1.8 in L4/L5 DRG between tumor-bearing and sham rats. Antisense oligodeoxynucleotides (ODNs) against Nav1.8 were administered intrathecally at 14-16 days after surgery to knock down Nav1.8 protein expression and changes in pain-related behavior were observed. Tumor-bearing rats exhibited mechanical hyperalgesia and ambulatory-evoked pain from day 7 after inoculation of Walker 256 cells. In the advanced stage of cancer pain (days 16-19 after surgery), normalized Nav1.8 mRNA levels assessed by real-time RT-PCR were significantly lower in ipsilateral L4/L5 DRG of tumor-bearing rats compared with the sham group. Western-blot showed that the total expression of Nav1.8 protein significantly decreased bilaterally in DRG of tumor-bearing rats. Furthermore, as revealed by immunofluorescence, only the expression of Nav1.8 protein in small neurons down regulated significantly in bilateral DRG of cancer pain rats. After administration of antisense ODNs against Nav1.8, Nav1.8 protein expression decreased significantly and tumor-bearing rats showed alleviated mechanical hyperalgesia and ambulatory-evoked pain. These

Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice.

Science.gov (United States)

Lim, Hee-Young; Albuquerque, Boris; Häussler, Annett; Myrczek, Thekla; Ding, Aihao; Tegeder, Irmgard

2012-04-01

Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Opposing dorsal/ventral stream dynamics during figure-ground segregation

NARCIS (Netherlands)

Wokke, M.E.; Scholte, H.S.; Lamme, V.A.F.

2014-01-01

The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist

A study of dorsal vein pattern for biometric security

African Journals Online (AJOL)

Nafiisah

ensure more reliable security, many biometric verification techniques have been developed .... 3.0 HA D DORSAL VEI PATTER AS A BIOMETRIC ... image for the back of the hand, and converted by a computer into a digital image that can be.

Characterisation of rebound depolarisation in mice deep dorsal horn neurons in vitro.

Science.gov (United States)

Rivera-Arconada, Ivan; Lopez-Garcia, Jose A

2015-09-01

Spinal dorsal horn neurons constitute the first relay for pain processing and participate in the processing of other sensory, motor and autonomic information. At the cellular level, intrinsic excitability is a factor contributing to network function. In turn, excitability is set by the array of ionic conductance expressed by neurons. Here, we set out to characterise rebound depolarisation following hyperpolarisation, a feature frequently described in dorsal horn neurons but never addressed in depth. To this end, an in vitro preparation of the spinal cord from mice pups was used combined with whole-cell recordings in current and voltage clamp modes. Results show the expression of H- and/or T-type currents in a significant proportion of dorsal horn neurons. The expression of these currents determines the presence of rebound behaviour at the end of hyperpolarising pulses. T-type calcium currents were associated to high-amplitude rebounds usually involving high-frequency action potential firing. H-currents were associated to low-amplitude rebounds less prone to elicit firing or firing at lower frequencies. For a large proportion of neurons expressing both currents, the H-current constitutes a mechanism to ensure a faster response after hyperpolarisations, adjusting the latency of the rebound firing. We conclude that rebound depolarisation and firing are intrinsic factors to many dorsal horn neurons that may constitute a mechanism to integrate somatosensory information in the spinal cord, allowing for a rapid switch from inhibited-to-excited states.

Root rots

Science.gov (United States)

Kathryn Robbins; Philip M. Wargo

1989-01-01

Root rots of central hardwoods are diseases caused by fungi that infect and decay woody roots and sometimes also invade the butt portion of the tree. By killing and decaying roots, root rotting fungi reduce growth, decrease tree vigor, and cause windthrow and death. The most common root diseases of central hardwoods are Armillaria root rot, lnonotus root rot, and...

Dietary fat level affecting histochemical radiosensitivity in dorsal aorta in rats

International Nuclear Information System (INIS)

Yousri, R.M.; Roushdy, H.M.; EL-Malkh, N.M.; Ashry, M.A.; Soliman, S.M.

1988-01-01

The present work has been conducted to investigate the effect of dietary fat status and/or cumulative whole body gamma radiation exposures up to 15 Gy the histochemical pattern of the dorsal aortas of male albino rats. Experimental animals were fed on either fat-rich or fat-free diet and the observations compared with those fed normal fat diet. The histochemical investigations has been confined to the concentration levels of mucopolysaccharide substance and total lipids. The dorsal aorta normal fat group showed higher content of PAS-positive material in the first two layers of the aorta wall in comparison with decreased amount of collagen fibers was shown in fat-rich group

Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers.

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Laedermann, Cédric J; Pertin, Marie; Suter, Marc R; Decosterd, Isabelle

2014-03-11

Dysregulation of voltage-gated sodium channels (Na(v)s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Na(v)s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na(v)s mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments. A strong downregulation was observed for every Na(v)s isoform expressed except for Na(v)1.2; even Na(v)1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Na(v)s were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Na(v)s isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG. The complex regulation of Na(v)s, together with the anatomical rostral shift of the DRG harboring injured

Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study.

Science.gov (United States)

Ulvi, Hızır; Demir, Recep; Aygül, Recep; Kotan, Dilcan; Calik, Muhammet; Aydin, Mehmet Dumlu

2013-12-30

Phrenic nerves have important roles on the management of respiration rhythm. Diaphragm paralysis is possible in phrenic nerve roots ischemia in subarachnoid hemorrhage (SAH). We examined whether there is a relationship between phrenic nerve root ischemia and respiratory disturbances in SAH. This study was conducted on 5 healthy control and 14 rabbits with experimentally induced SAH by injecting autologous blood into their cisterna magna. Animals were followed up via monitors for detecting the heart and respiration rhythms for 20 days and then decapitaed by humanely. Normal and degenerated neuron densities of phrenic nerve root at the level of C4 dorsal root ganglia (C4DRG) were estimated by Stereological methods. Between the mean numerical density of degenerated neurons of C4DRG and respiratory rate/minute of groups were compared statistically. Phrenic nerve roots, artery and diaphragm muscles degeneration was detected in respiratory arrest developed animals. The mean neuronal density of C4DRG was 13272 ±1201/mm3 with a mean respiration rate of 23 ±4/min in the control group. The mean degenerated neuron density was 2.240 ±450/mm(3) and respiration rhythm was 31 ±6/min in survivors. But, the mean degenerated neuron density was 5850 ±650/mm(3) and mean respiration rhythm was 34 ±7/min in respiratory arrest developed animals (n = 7). A linear relationship was noticed between the degenerated neuron density of C4DRG and respiraton rate (r = -0.758; p Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature.

Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

Science.gov (United States)

Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

2016-04-15

Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

Heterotaxy syndrome with associated agenesis of dorsal pancreas and polysplenia: A case report

Directory of Open Access Journals (Sweden)

Syed Althaf Ali1

2015-01-01

Full Text Available Heterotaxy syndrome is a rare embryological disorder comprising of polysplenia, partial agenesis of dorsal pancreas, malrotation of gut, cardiac and vascular anomalies resulting from failure of development of the usual left–right asymmetry of organs. We report a rare case of heterotaxy syndrome with polysplenia, partial agenesis of dorsal pancreas and malrotation of gut in a 28 year female presenting with subacute intestinal obstruction along with imaging illustrations, brief discussion and thorough review of literature.

Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

Science.gov (United States)

Contreras-Rodríguez, Oren; Martín-Pérez, Cristina; Vilar-López, Raquel; Verdejo-Garcia, Antonio

2017-05-01

The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Automatic phoneme category selectivity in the dorsal auditory stream.

Science.gov (United States)

Chevillet, Mark A; Jiang, Xiong; Rauschecker, Josef P; Riesenhuber, Maximilian

2013-03-20

Debates about motor theories of speech perception have recently been reignited by a burst of reports implicating premotor cortex (PMC) in speech perception. Often, however, these debates conflate perceptual and decision processes. Evidence that PMC activity correlates with task difficulty and subject performance suggests that PMC might be recruited, in certain cases, to facilitate category judgments about speech sounds (rather than speech perception, which involves decoding of sounds). However, it remains unclear whether PMC does, indeed, exhibit neural selectivity that is relevant for speech decisions. Further, it is unknown whether PMC activity in such cases reflects input via the dorsal or ventral auditory pathway, and whether PMC processing of speech is automatic or task-dependent. In a novel modified categorization paradigm, we presented human subjects with paired speech sounds from a phonetic continuum but diverted their attention from phoneme category using a challenging dichotic listening task. Using fMRI rapid adaptation to probe neural selectivity, we observed acoustic-phonetic selectivity in left anterior and left posterior auditory cortical regions. Conversely, we observed phoneme-category selectivity in left PMC that correlated with explicit phoneme-categorization performance measured after scanning, suggesting that PMC recruitment can account for performance on phoneme-categorization tasks. Structural equation modeling revealed connectivity from posterior, but not anterior, auditory cortex to PMC, suggesting a dorsal route for auditory input to PMC. Our results provide evidence for an account of speech processing in which the dorsal stream mediates automatic sensorimotor integration of speech and may be recruited to support speech decision tasks.

Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons.

Science.gov (United States)

Winland, Carissa D; Welsh, Nora; Sepulveda-Rodriguez, Alberto; Vicini, Stefano; Maguire-Zeiss, Kathleen A

2017-11-01

Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca 2+ ] i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca 2+ ] i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca 2+ ] i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca 2+ ] i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

Science.gov (United States)

Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

2017-08-10

Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Root growth, secondary root formation and root gravitropism in carotenoid-deficient seedlings of Zea mays L

Science.gov (United States)

Ng, Y. K.; Moore, R.

1985-01-01

The effect of ABA on root growth, secondary-root formation and root gravitropism in seedlings of Zea mays was investigated by using Fluridone-treated seedlings and a viviparous mutant, both of which lack carotenoids and ABA. Primary roots of seedlings grown in the presence of Fluridone grew significantly slower than those of control (i.e. untreated) roots. Elongation of Fluridone-treated roots was inhibited significantly by the exogenous application of 1 mM ABA. Exogenous application of 1 micromole and 1 nmole ABA had either no effect or only a slight stimulatory effect on root elongation, depending on the method of application. The absence of ABA in Fluridone-treated plants was not an important factor in secondary-root formation in seedlings less than 9-10 d old. However, ABA may suppress secondary-root formation in older seedlings, since 11-d-old control seedlings had significantly fewer secondary roots than Fluridone-treated seedlings. Roots of Fluridone-treated and control seedlings were graviresponsive. Similar data were obtained for vp-9 mutants of Z. mays, which are phenotypically identical to Fluridone-treated seedlings. These results indicate that ABA is necessary for neither secondary-root formation nor for positive gravitropism by primary roots.

An amphioxus Msx gene expressed predominantly in the dorsal neural tube.

Science.gov (United States)

Sharman, A C; Shimeld, S M; Holland, P W

1999-04-01

Genomic and cDNA clones of an Msx class homeobox gene were isolated from amphioxus (Branchiostoma floridae). The gene, AmphiMsx, is expressed in the neural plate from late gastrulation; in later embryos it is expressed in dorsal cells of the neural tube, excluding anterior and posterior regions, in an irregular reiterated pattern. There is transient expression in dorsal cells within somites, reminiscent of migrating neural crest cells of vertebrates. In larvae, mRNA is detected in two patches of anterior ectoderm proposed to be placodes. Evolutionary analyses show there is little phylogenetic information in Msx protein sequences; however, it is likely that duplication of Msx genes occurred in the vertebrate lineage.

Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

Science.gov (United States)

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

2011-01-01

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

Spiny Prey, Fortunate Prey. Dorsal Spines Are an Asset in Intraguild Interactions among Lady Beetles

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Louis Hautier

2017-11-01

Full Text Available The Multicolored Asian Ladybird, Harmonia axyridis, is an extremely successful invasive species. Here we suggest that, in addition to many other traits, the dorsal spines of its larvae contribute to their success, as suggested by behavioral observations of agonistic interactions between H. axyridis and European coccinellids. In coccinellids, the role of dorsal spines in these interactions has been poorly studied and they could be a physical protection against intraguild predators. Dorsal spines of second instar H. axyridis larvae were removed with micro-scissors, which resulted in spineless larvae after molting (spineless group. These larvae were then exposed to starved Coccinella septempunctata larvae. Two control categories were also submitted to interactions: H. axyridis larvae with all their spines (control group and with their spines, but injured by pin stings (injured group. Spine removal at the second instar did not hamper H. axyridis development. The bite rate by C. septempunctata was significantly higher on the spineless H. axyridis and more dorsally located compared to the control and injured groups, while no bite rate difference was observed between the injured and the control group. Our results suggest that in addition to behavioral and chemical defenses, the dorsal spines play a significant protective role against bites. Therefore, spines in ladybirds could be considered as a morphological defense against intraguild predation. In H. axyridis, these defenses might contribute to its success in food resources already exploited by other guild members and thus further facilitate the invasion of new areas.

Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo

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Clemente, Cristina; Montalvo, María Gregoria; Seiki, Motoharu; Arroyo, Alicia G.

2017-01-01

Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo. Here, we report a detailed expression analysis of Mt4-mmp during mouse embryonic development by using a LacZ reporter transgenic mouse line. We showed that Mt4-mmp is detected from early stages of development to postnatal stages following a dynamic and restricted pattern of expression. Mt4-mmp was first detected at E8.5 limited to the intersomitic vascularization, the endocardial endothelium and the dorsal aorta. Mt4-mmpLacZ/+ cells were also observed in the neural crest cells, somites, floor plate and notochord at early stages. From E10.5, expression localized in the limb buds and persists during limb development. A strong expression in the brain begins at E12.5 and continues to postnatal stages. Specifically, staining was observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, septum, dorsal thalamus and the spinal cord. In addition, LacZ-positive cells were also detected during eye development, initially at the hyaloid artery and later on located in the lens and the neural retina. Mt4-mmp expression was confirmed by quantitative RT-PCR and western blot analysis in some embryonic tissues. Our data point to distinct functions for this metalloproteinase during embryonic development, particularly during brain formation, angiogenesis and limb development. PMID:28926609

Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

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Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

2018-07-01

The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

Treatment of acute and subacute dorsal perilunate fracture dislocations

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Levent Kucuk

2014-04-01

Outcomes: Results of the perilunate fracture dislocations treated in acute or subacute phase by open reduction and internal fixation via dorsal approach are satisfactory. There is a strong demand for prospective, randomized studies to compare the results of different treatment modalities. [Hand Microsurg 2014; 3(1.000: 1-7

Role of motor-evoked potential monitoring in conjunction with temporary clipping of spinal nerve roots in posterior thoracic spine tumor surgery.

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Eleraky, Mohammed A; Setzer, Matthias; Papanastassiou, Ioannis D; Baaj, Ali A; Tran, Nam D; Katsares, Kiesha M; Vrionis, Frank D

2010-05-01

The vascular supply of the thoracic spinal cord depends on the thoracolumbar segmental arteries. Because of the small size and ventral course of these arteries in relation to the dorsal root ganglion and ventral root, they cannot be reliably identified during surgery by anatomic or morphologic criteria. Sacrificing them will most likely result in paraplegia. The goal of this study was to evaluate a novel method of intraoperative testing of a nerve root's contribution to the blood supply of the thoracic spinal cord. This is a clinical retrospective study of 49 patients diagnosed with thoracic spine tumors. Temporary nerve root clipping combined with motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring was performed; additionally, postoperative clinical evaluation was done and reported in all cases. All cases were monitored by SSEP and MEPs. The nerve root to be sacrificed was temporarily clipped using standard aneurysm clips, and SSEP/MEP were assessed before and after clipping. Four nerve roots were sacrificed in four cases, three nerve roots in eight cases, and two nerve roots in 22 cases. Nerve roots were sacrificed bilaterally in 12 cases. Most patients (47/49) had no changes in MEP/SSEP and had no neurological deficit postoperatively. One case of a spinal sarcoma demonstrated changes in MEP after temporary clipping of the left T11 nerve root. The nerve was not sacrificed, and the patient was neurologically intact after surgery. In another case of a sarcoma, MEPs changed in the lower limbs after ligation of left T9 nerve root. It was felt that it was a global event because of anesthesia. Postoperatively, the patient had complete paraplegia but recovered almost completely after 6 months. Temporary nerve root clipping combined with MEP and SSEP monitoring may enhance the impact of neuromonitoring in the intraoperative management of patients with thoracic spine tumors and favorably influence neurological outcome. Copyright 2010 Elsevier

Patterning of the dorsal-ventral axis in echinoderms: insights into the evolution of the BMP-chordin signaling network.

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François Lapraz

2009-11-01

Full Text Available Formation of the dorsal-ventral axis of the sea urchin embryo relies on cell interactions initiated by the TGFbeta Nodal. Intriguingly, although nodal expression is restricted to the ventral side of the embryo, Nodal function is required for specification of both the ventral and the dorsal territories and is able to restore both ventral and dorsal regions in nodal morpholino injected embryos. The molecular basis for the long-range organizing activity of Nodal is not understood. In this paper, we provide evidence that the long-range organizing activity of Nodal is assured by a relay molecule synthesized in the ventral ectoderm, then translocated to the opposite side of the embryo. We identified this relay molecule as BMP2/4 based on the following arguments. First, blocking BMP2/4 function eliminated the long-range organizing activity of an activated Nodal receptor in an axis rescue assay. Second, we demonstrate that BMP2/4 and the corresponding type I receptor Alk3/6 functions are both essential for specification of the dorsal region of the embryo. Third, using anti-phospho-Smad1/5/8 immunostaining, we show that, despite its ventral transcription, the BMP2/4 ligand triggers receptor mediated signaling exclusively on the dorsal side of the embryo, one of the most extreme cases of BMP translocation described so far. We further report that the pattern of pSmad1/5/8 is graded along the dorsal-ventral axis and that two BMP2/4 target genes are expressed in nested patterns centered on the region with highest levels of pSmad1/5/8, strongly suggesting that BMP2/4 is acting as a morphogen. We also describe the very unusual ventral co-expression of chordin and bmp2/4 downstream of Nodal and demonstrate that Chordin is largely responsible for the spatial restriction of BMP2/4 signaling to the dorsal side. Thus, unlike in most organisms, in the sea urchin, a single ventral signaling centre is responsible for induction of ventral and dorsal cell fates. Finally

Management of generalized spasticity of lower limbs by selective ...

African Journals Online (AJOL)

Wael Fouad

2011-08-09

Aug 9, 2011 ... All cases underwent MDT that consisted of a longitudinal incision of the ... The methods of surgical management are classified accord- ... nerves, dorsal roots, dorsal root entry zone or spinal cord.7,8 ... bedridden and totally dependent patient). ... paraplegia of cerebral origin include cerebral palsy, cerebro-.

Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury

NARCIS (Netherlands)

Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R.; Ljubkovic, Marko; Mueller, Samantha J.; Stucky, Cheryl L.; Hogan, Quinn H.

2013-01-01

The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

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Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.

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Hasegawa, Emi; Maejima, Takashi; Yoshida, Takayuki; Masseck, Olivia A; Herlitze, Stefan; Yoshioka, Mitsuhiro; Sakurai, Takeshi; Mieda, Michihiro

2017-04-25

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.

Morphology of the dorsal and lateral calcaneocuboid ligaments.

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Dorn-Lange, Nadja V; Nauck, Tanja; Lohrer, Heinz; Arentz, Sabine; Konerding, Moritz A

2008-09-01

The dorsolateral calcaneocuboid ligaments have different configurations. In the literature they are only described as either the dorsal or lateral calcaneocuboid ligament. However, recent reconstructive surgical techniques may benefit from a better understanding of the anatomy. The aims of this study were to classify the morphology and attachments of the dorso-lateral calcaneocuboid ligaments and to determine their dimensions. The dorso-lateral aspects of the calcaneocuboid joint of 30 cadaver feet were dissected to expose the associated ligaments. Further, we evaluated possible bony landmarks of the calcaneus that could imply which shape or course the ligament would have in a specific individual. Our findings showed a wide variety of configurations in shape, number, and attachment sites. A constant dorsal ligament and an additional narrower lateral ligament was detectable in half of the cases. The majority of the dorso-lateral calcaneocuboid ligament-complex had an upward course and fanning out from proximal to distal. No bony predictor for the ligaments' shape or course was found. The dorso-lateral ligament-complex of the calcaneocuboid joint revealed a wide variety of configurations. Better understanding of the anatomy of these ligaments may aid in the anatomic reconstruction of these ligaments.

History and evolution of dorsal onlay urethroplasty for bulbar urethral stricture repair using skin or buccal mucosal grafts.

Science.gov (United States)

Barbagli, G; Lazzeri, M

2007-01-01

OBJECTIVES. To illustrate the history and the evolution over time of bulbar dorsal onlay urethroplasty, comparing outcomes when using buccal mucosa or skin grafts. MATERIALS AND METHODS. Ninety-four patients underwent bulbar urethral reconstruction using two dorsal onlay techniques, namely augmented anastomotic urethroplasty and dorsal onlay graft urethroplasty. Preoperative evaluation included clinical history, physical examination, urine culture, residual urine measurement, uroflowmetry and urethrography. Thirty-four patients underwent augmented anastomotic urethroplasty using penile skin (10 cases) or buccal mucosa (24 cases) grafts. Sixty patients underwent dorsal onlay graft urethroplasty using penile skin (38 cases) or buccal mucosa (22 cases) grafts. Forty-eight out of 94 patients received skin grafts and 46 buccal mucosal grafts. RESULTS. Sixty-four (68%) out of 94 cases were successful, whereas 30 (32%) failed. The 34 augmented anastomotic urethroplasties provided successful outcomes in 24 cases (70.6%), but poor outcomes in 10 (29.4%) cases. The 60 dorsal onlay graft urethroplasty proved to be successful in 42 cases (70%), failing in 18 (30%) cases. Twenty-eight (58.3%) out of 48 penile skin grafts were successful and 20 (41.7%) failed. Thirty-six (78.3%) out of 46 buccal mucosa grafts were successful and 10 (21.7%) failed. The 30 failed cases were then treated with internal urethrotomy in 14 cases (46.7%), perineal urethrostomy in 8 cases (26.7%), two-stage repair in 4 cases (13.3%), and one-stage repair in 4 cases (13.3%). CONCLUSIONS. The dorsal onlay technique used for bulbar urethral stricture repair has changed over time. In our experience, the buccal mucosa seems to be the best substitute graft material for bulbar urethroplasty using dorsal approach.

Complex population response of dorsal putamen neurons predicts the ability to learn.

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Laquitaine, Steeve; Piron, Camille; Abellanas, David; Loewenstein, Yonatan; Boraud, Thomas

2013-01-01

Day-to-day variability in performance is a common experience. We investigated its neural correlate by studying learning behavior of monkeys in a two-alternative forced choice task, the two-armed bandit task. We found substantial session-to-session variability in the monkeys' learning behavior. Recording the activity of single dorsal putamen neurons we uncovered a dual function of this structure. It has been previously shown that a population of neurons in the DLP exhibits firing activity sensitive to the reward value of chosen actions. Here, we identify putative medium spiny neurons in the dorsal putamen that are cue-selective and whose activity builds up with learning. Remarkably we show that session-to-session changes in the size of this population and in the intensity with which this population encodes cue-selectivity is correlated with session-to-session changes in the ability to learn the task. Moreover, at the population level, dorsal putamen activity in the very beginning of the session is correlated with the performance at the end of the session, thus predicting whether the monkey will have a "good" or "bad" learning day. These results provide important insights on the neural basis of inter-temporal performance variability.

Agenesis of the dorsal pancreas: systematic review of a clinical challenge

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Javier A. Cienfuegos

Full Text Available Background: Agenesis of the dorsal pancreas is a rare malformation. Since 1911 and until 2008, 53 cases have been reported. Several authors have recently described the association of this anomaly with neoplasia of the ventral pancreas, thus we performed a systematic review of the literature from 2008 to 2015. Methods: A systematic review of the Medline and ISI Web of Science Databases from 2008 until 2015 was carried out, and 30 articles which met the inclusion criteria were identified that included a total of 53 patients: 7 children and 46 adults. Conclusions: Although dorsal pancreatic agenesis is a rare malformation, given its association with non-alcoholic pancreatitis and neoplasia of the residual pancreas, physicians should maintain an expectant attitude.

Propagation of a dorsal cortical fracture of the third metacarpal bone in two horses

International Nuclear Information System (INIS)

Spurlock, G.H.

1988-01-01

Seemingly, propagation of a dorsal cortical fracture in the third metacarpal bone developed after continued race performance in 2 horses. Historically, both horses had intermittent lameness that had responded to nonsteroidal anti-inflammatory drugs and brief rest periods. However, lameness in both horses had increased in severity. Radiography revealed a dorsal cortical fracture of the third metacarpal bone, with propagation of the fracture plane proximally. Fractures were incomplete and healed with stall rest in both horses

Influence of needle position on lumbar segmental nerve root block selectivity.

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Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

Root development during soil genesis: effects of root-root interactions, mycorrhizae, and substrate

Science.gov (United States)

Salinas, A.; Zaharescu, D. G.

2015-12-01

A major driver of soil formation is the colonization and transformation of rock by plants and associated microbiota. In turn, substrate chemical composition can also influence the capacity for plant colonization and development. In order to better define these relationships, a mesocosm study was set up to analyze the effect mycorrhizal fungi, plant density and rock have on root development, and to determine the effect of root morphology on weathering and soil formation. We hypothesized that plant-plant and plant-fungi interactions have a stronger influence on root architecture and rock weathering than the substrate composition alone. Buffalo grass (Bouteloua dactyloides) was grown in a controlled environment in columns filled with either granular granite, schist, rhyolite or basalt. Each substrate was given two different treatments, including grass-microbes and grass-microbes-mycorrhizae and incubated for 120, 240, and 480 days. Columns were then extracted and analyzed for root morphology, fine fraction, and pore water major element content. Preliminary results showed that plants produced more biomass in rhyolite, followed by schist, basalt, and granite, indicating that substrate composition is an important driver of root development. In support of our hypothesis, mycorrhizae was a strong driver of root development by stimulating length growth, biomass production, and branching. However, average root length and branching also appeared to decrease in response to high plant density, though this trend was only present among roots with mycorrhizal fungi. Interestingly, fine fraction production was negatively correlated with average root thickness and volume. There is also slight evidence indicating that fine fraction production is more related to substrate composition than root morphology, though this data needs to be further analyzed. Our hope is that the results of this study can one day be applied to agricultural research in order to promote the production of crops

Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord

NARCIS (Netherlands)

Zhang, Yi; Zhang, Xinyu; Wu, Dongsheng; Verhaagen, J.; Richardson, Peter M; Yeh, John; Bo, Xuenong

2007-01-01

In adult mammals, sensory axons that regenerate in the dorsal root are unable to grow across the dorsal root entry zone (DREZ) into the spinal cord. In this study we examined whether, by inducing expression of polysialic acid (PSA) (a large carbohydrate attached to molecules on the cell surface), in

Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

Science.gov (United States)

Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

2014-01-01

The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

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Kazuhiko Nishida

Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

Science.gov (United States)

Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

2015-08-30

Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dorsal and ventral streams across sensory modalities

Institute of Scientific and Technical Information of China (English)

Anna Sedda; Federica Scarpina

2012-01-01

In this review,we describe the current models of dorsal and ventral streams in vision,audition and touch.Available theories take their first steps from the model of Milner and Goodale,which was developed to explain how human actions can be efficiently carried out using visual information.Since then,similar concepts have also been applied to other sensory modalities.We propose that advances in the knowledge of brain functioning can be achieved through models explaining action and perception patterns independently from sensory modalities.

The action of chlorphenesin carbamate on the frog spinal cord.

Science.gov (United States)

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

The Locus Coeruleus–Norepinephrine System Mediates Empathy for Pain through Selective Up-Regulation of P2X3 Receptor in Dorsal Root Ganglia in Rats

Directory of Open Access Journals (Sweden)

Yun-Fei Lü

2017-09-01

Full Text Available Empathy for pain (vicariously felt pain, an ability to feel, recognize, understand and share the painful emotions of others, has been gradually accepted to be a common identity in both humans and rodents, however, the underlying neural and molecular mechanisms are largely unknown. Recently, we have developed a rat model of empathy for pain in which pain can be transferred from a cagemate demonstrator (CD in pain to a naïve cagemate observer (CO after 30 min dyadic priming social interaction. The naïve CO rats display both mechanical pain hypersensitivity (hyperalgesia and enhanced spinal nociception. Chemical lesions of bilateral medial prefrontal cortex (mPFC abolish the empathic pain response completely, suggesting existence of a top-down facilitation system in production of empathy for pain. However, the social transfer of pain was not observed in non-cagemate observer (NCO after dyadic social interaction with a non-cagemate demonstrator (NCD in pain. Here we showed that dyadic social interaction with a painful CD resulted in elevation of circulating norepinephrine (NE and increased neuronal activity in the locus coeruleus (LC in the CO rats. Meanwhile, CO rats also had over-expression of P2X3, but not TRPV1, in the dorsal root ganglia (DRG. Chemical lesion of the LC-NE neurons by systemic DSP-4 and pharmacological inhibition of central synaptic release of NE by clonidine completely abolished increase in circulating NE and P2X3 receptor expression, as well as the sympathetically-maintained development of empathic mechanical hyperalgesia. However, in the NCO rats, neither the LC-NE neuronal activity nor the P2X3 receptor expression was altered after dyadic social interaction with a painful NCD although the circulating corticosterone and NE were elevated. Finally, in the periphery, both P2X3 receptor and α1 adrenergic receptor were found to be involved in the development of empathic mechanical hyperalgesia. Taken together with our previous

Burst-generating neurones in the dorsal horn in an in vitro preparation of the turtle spinal cord

DEFF Research Database (Denmark)

Russo, R E; Hounsgaard, J

1996-01-01

1. In transverse slices of the spinal cord of the turtle, intracellular recordings were used to characterize and analyse the responses to injected current and activation of primary afferents in dorsal horn neurones. 2. A subpopulation of neurones, with cell bodies located centrally in the dorsal...

Dorsal approaches to intradural extramedullary tumors of the craniovertebral junction

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D Refai

2010-01-01

Full Text Available Tumors of the craniovertebral junction (CVJ pose significant challenges to cranial and spine surgeons. Familiarity with the complex anatomy and avoidance of injury to neurologic and vascular structures are essential to success. Multiple surgical approaches to address lesions at the CVJ have been promoted, including ventral and dorsal-based trajectories. However, optimal selection of the surgical vector to manage the pathology requires a firm understanding of the limitations and advantages of each approach. The selection of the best surgical trajectory must include several factors, such as obtaining the optimal exposure of the region of interest, avoiding injury to critical neurologic or vascular structures, identification of normal anatomical landmarks, the familiarity and comfort level of the surgeon to the approach, and the need for fixation. This review article focuses on dorsal approaches to the CVJ and the advantages and limitations in managing intradural extramedullary tumors.

Rooting gene trees without outgroups: EP rooting.

Science.gov (United States)

Sinsheimer, Janet S; Little, Roderick J A; Lake, James A

2012-01-01

Gene sequences are routinely used to determine the topologies of unrooted phylogenetic trees, but many of the most important questions in evolution require knowing both the topologies and the roots of trees. However, general algorithms for calculating rooted trees from gene and genomic sequences in the absence of gene paralogs are few. Using the principles of evolutionary parsimony (EP) (Lake JA. 1987a. A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony. Mol Biol Evol. 4:167-181) and its extensions (Cavender, J. 1989. Mechanized derivation of linear invariants. Mol Biol Evol. 6:301-316; Nguyen T, Speed TP. 1992. A derivation of all linear invariants for a nonbalanced transversion model. J Mol Evol. 35:60-76), we explicitly enumerate all linear invariants that solely contain rooting information and derive algorithms for rooting gene trees directly from gene and genomic sequences. These new EP linear rooting invariants allow one to determine rooted trees, even in the complete absence of outgroups and gene paralogs. EP rooting invariants are explicitly derived for three taxon trees, and rules for their extension to four or more taxa are provided. The method is demonstrated using 18S ribosomal DNA to illustrate how the new animal phylogeny (Aguinaldo AMA et al. 1997. Evidence for a clade of nematodes, arthropods, and other moulting animals. Nature 387:489-493; Lake JA. 1990. Origin of the metazoa. Proc Natl Acad Sci USA 87:763-766) may be rooted directly from sequences, even when they are short and paralogs are unavailable. These results are consistent with the current root (Philippe H et al. 2011. Acoelomorph flatworms are deuterostomes related to Xenoturbella. Nature 470:255-260).

Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder

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Liu Dongjuan

2012-11-01

Full Text Available Abstract Introduction Post-traumatic stress disorder (PTSD is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS. The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter. Methods In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM. Levels of Cytochrome c (Cyt-C was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM. The change of thiamine monophosphatase (TMP levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM. Results Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS. Conclusions The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated

RootJS: Node.js Bindings for ROOT 6

Science.gov (United States)

Beffart, Theo; Früh, Maximilian; Haas, Christoph; Rajgopal, Sachin; Schwabe, Jonas; Wolff, Christoph; Szuba, Marek

2017-10-01

We present rootJS, an interface making it possible to seamlessly integrate ROOT 6 into applications written for Node.js, the JavaScript runtime platform increasingly commonly used to create high-performance Web applications. ROOT features can be called both directly from Node.js code and by JIT-compiling C++ macros. All rootJS methods are invoked asynchronously and support callback functions, allowing non-blocking operation of Node.js applications using them. Last but not least, our bindings have been designed to platform-independent and should therefore work on all systems supporting both ROOT 6 and Node.js. Thanks to rootJS it is now possible to create ROOT-aware Web applications taking full advantage of the high performance and extensive capabilities of Node.js. Examples include platforms for the quality assurance of acquired, reconstructed or simulated data, book-keeping and e-log systems, and even Web browser-based data visualisation and analysis.

Evaluation of bacterial leakage of four root- end filling materials: Gray Pro Root MTA, White Pro Root MTA, Root MTA and Portland Cement (type I

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Zarabian M.

2005-07-01

Full Text Available Background and Aim: Today several materials have been used for root- end filling in endodontic surgery. Optimal properties of Pro Root MTA in in-vitro and in-vivo studies has been proven. On the other hand, based on some studies, Root MTA (Iranian Pro Root MTA and Portland cement are similar to Pro Root MTA in physical and biologic properties. The aim of this study was to evaluate bacterial leakage (amount and mean leakage time of four root- end filling materials. Materials and Methods: In this experimental in-vitro study, seventy six extracted single- rooted human teeth were randomly divided into six groups for root-end filling with gray Pro Root MTA, white Pro Root MTA, Root MTA (Iranian Pro Root MTA, Portland Cement (type I and positive and negative control groups. Root canals were instrumented using the step- back technique. Root- end filling materials were placed in 3mm ultra sonic retro preparations. Samples and microleakage model system were sterilized in autoclave. The apical 3-4 mm of the roots were immersed in phenol red with 3% lactose broth culture medium. The coronal access of each specimen was inoculated every 24h with a suspension of Streptococcus sanguis (ATCC 10556. Culture media were observed every 24h for colour change indicating bacterial contamination for 60 days. Statistical analysis was performed using log- rank test with P<0.05 as the limit of significance. Results: At the end of study 50%, 56.25%, 56.25% and 50% of specimens filled with Gray Pro Root MTA, White Pro Root MTA. Root MTA and Portland Cement (type I had evidence of leakage respectively. The mean leakage time was 37.19±6.29, 36.44±5.81, 37.69±5.97 and 34.81±6.67 days respectively. Statistical analysis of data showed no significant difference among the leakage (amount and mean leakage time of the four tested root- end filling materials (P=0.9958. Conclusion: Based on the results of this study, there were no significant differences in leakage among the four

Inflammatory reaction of the anterior dorsal tongue presumably to sodium lauryl sulfate within toothpastes: a triple case report.

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Brown, Ronald S; Smith, Langston; Glascoe, Alison L

2018-02-01

Sodium lauryl sulfate (SLS), a popular surface active agent ingredient within toothpastes, is known for its foaming action. Surface active agents increase the effectiveness of toothpastes with respect to dental plaque removal. SLS is a known irritant and also has allergenic potential. The authors report 3 patients with oral pain secondary to inflammation of the dorsal anterior tongue. These patients were all using toothpastes with SLS as an ingredient. The dorsal tongue lesions and oral pain resolved upon switching to toothpastes without SLS as an ingredient. Clinicians should be aware of the potential of SLS within toothpastes to cause oral mucosal inflammatory reactions of the anterior dorsal tongue. To our knowledge, these are the first case reports of oral mucosal inflammatory reactions of the anterior dorsal tongue associated with SLS containing toothpastes. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural Graphical Lasso for Learning Mouse Brain Connectivity

KAUST Repository

Yang, Sen

2015-08-07

Investigations into brain connectivity aim to recover networks of brain regions connected by anatomical tracts or by functional associations. The inference of brain networks has recently attracted much interest due to the increasing availability of high-resolution brain imaging data. Sparse inverse covariance estimation with lasso and group lasso penalty has been demonstrated to be a powerful approach to discover brain networks. Motivated by the hierarchical structure of the brain networks, we consider the problem of estimating a graphical model with tree-structural regularization in this paper. The regularization encourages the graphical model to exhibit a brain-like structure. Specifically, in this hierarchical structure, hundreds of thousands of voxels serve as the leaf nodes of the tree. A node in the intermediate layer represents a region formed by voxels in the subtree rooted at that node. The whole brain is considered as the root of the tree. We propose to apply the tree-structural regularized graphical model to estimate the mouse brain network. However, the dimensionality of whole-brain data, usually on the order of hundreds of thousands, poses significant computational challenges. Efficient algorithms that are capable of estimating networks from high-dimensional data are highly desired. To address the computational challenge, we develop a screening rule which can quickly identify many zero blocks in the estimated graphical model, thereby dramatically reducing the computational cost of solving the proposed model. It is based on a novel insight on the relationship between screening and the so-called proximal operator that we first establish in this paper. We perform experiments on both synthetic data and real data from the Allen Developing Mouse Brain Atlas; results demonstrate the effectiveness and efficiency of the proposed approach.

[Trombosis of the dorsal penis vein (of Mondor's phlebitis). Presentation of a new case].

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Rodríguez Faba, O; Parra Muntaner, L; Gómez Cisneros, S C; Martín Benito, J L; Escaf Barmadah, S

2006-01-01

We present a new case of trombosis of the superficial dorsal penis vein called Penile Mondor's disease. The characteristics of the disease are reviewed and the most usual diagnostic and therapeutic methods. The case of a 41 year old man is reviewed who consulted for pain and induration on the proximal part of the penis. After phisical examination and Eco-doppler was made the diagnosis of Mondor's disease. He receibed treatment with non steroidal antiinflamatories and antibiotics. The dorsal vein thrombosis is a rare disease with pain an induration of the dorsal part of the penis. The ethiology can be traumatic, neoplasic, excesive sexual activity or abstinence. Is necesary the diferencial diagnosis with esclerosant linphangitis and the most important imaging is the Eco-doppler. The treatment is based in non steroidal antiinflamatories and antibiotics wit infection. The local aplication of heparine can be useful and the surgery with thrombectomy and resection is for persistent cases.

Root proliferation in decaying roots and old root channels: A nutrient conservation mechanism in oligotrophic mangrove forests?

Science.gov (United States)

McKee, K.L.

2001-01-01

1. In oligotrophic habitats, proliferation of roots in nutrient-rich microsites may contribute to overall nutrient conservation by plants. Peat-based soils on mangrove islands in Belize are characterized by the presence of decaying roots and numerous old root channels (0.1-3.5 cm diameter) that become filled with living and highly branched roots of Rhizophora mangle and Avicennia germinans. The objectives of this study were to quantify the proliferation of roots in these microsites and to determine what causes this response. 2. Channels formed by the refractory remains of mangrove roots accounted for only 1-2% of total soil volume, but the proportion of roots found within channels varied from 9 to 24% of total live mass. Successive generations of roots growing inside increasingly smaller root channels were also found. 3. When artificial channels constructed of PVC pipe were buried in the peat for 2 years, those filled with nutrient-rich organic matter had six times more roots than empty or sand-filled channels, indicating a response to greater nutrient availability rather than to greater space or less impedance to root growth. 4. Root proliferation inside decaying roots may improve recovery of nutrients released from decomposing tissues before they can be leached or immobilized in this intertidal environment. Greatest root proliferation in channels occurred in interior forest zones characterized by greater soil waterlogging, which suggests that this may be a strategy for nutrient capture that minimizes oxygen losses from the whole root system. 5. Improved efficiency of nutrient acquisition at the individual plant level has implications for nutrient economy at the ecosystem level and may explain, in part, how mangroves persist and grow in nutrient-poor environments.

Dorsal and ventral changes of the occipital vertebrae

International Nuclear Information System (INIS)

Banki, Z.

1981-01-01

Based on his own observation and on the literature, the author discusses various types of calcification in the occipital-cervical region, beginning with those situated dorsally and followed by ventral forms. An attempt is made to classify these changes, depending on their morphology and situation, from an embryological point of view. The pro-atlantal and ante pro-atlanto origin of the occipital vertebrae is discussed. Differentiation depends on appearances. (orig.) [de

Social conflict resolution regulated by two dorsal habenular subregions in zebrafish.

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Chou, Ming-Yi; Amo, Ryunosuke; Kinoshita, Masae; Cherng, Bor-Wei; Shimazaki, Hideaki; Agetsuma, Masakazu; Shiraki, Toshiyuki; Aoki, Tazu; Takahoko, Mikako; Yamazaki, Masako; Higashijima, Shin-ichi; Okamoto, Hitoshi

2016-04-01

When animals encounter conflict they initiate and escalate aggression to establish and maintain a social hierarchy. The neural mechanisms by which animals resolve fighting behaviors to determine such social hierarchies remain unknown. We identified two subregions of the dorsal habenula (dHb) in zebrafish that antagonistically regulate the outcome of conflict. The losing experience reduced neural transmission in the lateral subregion of dHb (dHbL)-dorsal/intermediate interpeduncular nucleus (d/iIPN) circuit. Silencing of the dHbL or medial subregion of dHb (dHbM) caused a stronger predisposition to lose or win a fight, respectively. These results demonstrate that the dHbL and dHbM comprise a dual control system for conflict resolution of social aggression. Copyright © 2016, American Association for the Advancement of Science.

Perineuronal nets play a role in regulating striatal function in the mouse.

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Hyunchul Lee

Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

Perineuronal nets play a role in regulating striatal function in the mouse.

Science.gov (United States)

Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu

2012-01-01

The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

Comparison of efficacy of continuous epidural block and pulsed radiofrequency to the dorsal root ganglion for management of pain persisting beyond the acute phase of herpes zoster.

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Eung Don Kim

Full Text Available There is little evidence regarding the effectiveness of intervention methods in the treatment of zoster-related pain (ZAP after the acute phase of zoster. Generally, if ZAP remains after more than 180 days from its onset, the likelihood of pain reduction is very low; this condition is considered as a "well established" post-herpetic neuralgia (PHN. Although the clinical efficacy of intrathecal steroid injection and spinal cord stimulation (SCS for ZAP management has been reported, these interventions are not widely used due to inherent disadvantages. Continuous epidural block is widely used in clinical practice, and the effectiveness of pulsed radiofrequency (PRF to the dorsal root ganglion (DRG in the treatment of ZAP already has been reported.The purpose of this study was to compare the clinical efficacy of continuous epidural block and DRG PRF beyond acute phase of zoster, bur before PHN was well established (from 30 days to180 days after zoster onset.Retrospective comparative study.A total of 42 medical records were analyzed. Patients were divided into two groups according to the type of procedure utilized: continuous epidural block (continuous epidural group and DRG PRF (PRF group. The clinical efficacy of the procedure was evaluated using a numeric rating scale (NRS and the medication dose before and 1 to 6 months after the procedure.There was a significant decrease in the NRS value with time in both groups. However, this decrease was more significant in the PRF group than in the continuous epidural group. The medication doses decreased significantly in the PRF group over time, but not in the continuous epidural group. The rate of clinically meaningful PHN (NRS≥3 was also lower in the PRF group than in the continuous epidural group.This study revealed that DRG PRF was more effective than a continuous epidural block in treating ZAP after the acute phase of zoster. A neuromodulation method such as DRG PRF may be a useful option for

Neurogenesis in spinal cord of mouse: an autoradiographic analysis

International Nuclear Information System (INIS)

Nornes, H.O.; Carry, M.

1978-01-01

An autoradiographic analysis of the time and sites of origin, and the migration and setting patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10-15 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10-11 of gestation; the neurons in the intermediate gray region originated on days 11-14 of gestation; the neurons of the head of the dorsal horn originated on days 12-14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12-14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord. (Auth.)

Comparison of dorsal and dorsomedial displacement in evaluation of first ray hypermobility in feet with and without hallux valgus.

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Singh, Dishan; Biz, Carlo; Corradin, Marco; Favero, Laura

2016-06-01

Hypermobility of the first ray, a probable primary cause of hallux valgus, has traditionally been evaluated in the dorsal direction only although the first tarso-metatarsal joint allows movement in a dorso-medial direction. 600 feet, divided according to the presence or absence of hallux valgus, were evaluated for both dorsal and dorso-medial displacement using a Klaue device. In the control group, the mean first ray displacement was 7.2mm (4.2-11.3) in the dorsal direction (sagittal plane) and 8.3mm (4.0-12.6) in the 45° dorso-medial direction. In the hallux valgus group, the mean first ray mobility was 9.8mm (5.2-14.1) in the dorsal direction compared to a mean of 11.0mm (5.9-16.2) in the 45° dorso-medial direction. It is a paradox that hypermobility of the first ray is measured in only a dorsal (vertical) direction whereas a hallux valgus angle and an intermetatarsal angle are only measured in a transverse plane. Furthermore, the weightbearing foot pronates during gait and the first metatarsal is displaced in a dorsomedial direction rather than a pure dorsal direction. It is suggested that measurement hypermobility of the first ray at a 45° dorso-medial direction is more appropriate. Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Complementary Gli activity mediates early patterning of the mouse visual system.

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Furimsky, Marosh; Wallace, Valerie A

2006-03-01

The Sonic hedgehog (Shh) signaling pathway plays a key role in the development of the vertebrate central nervous system, including the eye. This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes. In this study, we investigated the roles of the three vertebrate Glis in mediating midline Shh signaling in early ocular development. We examined the ocular phenotypes of Shh and Gli combination mutant mouse embryos and monitored proximodistal and dorsoventral patterning by the expression of specific eye development regulatory genes using in situ hybridization. We show that midline Shh signaling relieves the repressor activity of Gli3 adjacent to the midline and then promotes eye pattern formation through the nonredundant activities of all three Gli proteins. Gli3, in particular, is required to specify the dorsal optic stalk and to define the boundary between the optic stalk and the optic cup.

Elasticity maps of living neurons measured by combined fluorescence and atomic force microscopy.

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Spedden, Elise; White, James D; Naumova, Elena N; Kaplan, David L; Staii, Cristian

2012-09-05

Detailed knowledge of mechanical parameters such as cell elasticity, stiffness of the growth substrate, or traction stresses generated during axonal extensions is essential for understanding the mechanisms that control neuronal growth. Here, we combine atomic force microscopy-based force spectroscopy with fluorescence microscopy to produce systematic, high-resolution elasticity maps for three different types of live neuronal cells: cortical (embryonic rat), embryonic chick dorsal root ganglion, and P-19 (mouse embryonic carcinoma stem cells) neurons. We measure how the stiffness of neurons changes both during neurite outgrowth and upon disruption of microtubules of the cell. We find reversible local stiffening of the cell during growth, and show that the increase in local elastic modulus is primarily due to the formation of microtubules. We also report that cortical and P-19 neurons have similar elasticity maps, with elastic moduli in the range 0.1-2 kPa, with typical average values of 0.4 kPa (P-19) and 0.2 kPa (cortical). In contrast, dorsal root ganglion neurons are stiffer than P-19 and cortical cells, yielding elastic moduli in the range 0.1-8 kPa, with typical average values of 0.9 kPa. Finally, we report no measurable influence of substrate protein coating on cell body elasticity for the three types of neurons. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp.

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Ren, Qian; Huang, Xin; Cui, Yalei; Sun, Jiejie; Wang, Wen; Zhang, Xiaobo

2017-04-15

In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp ( Marsupenaeus japonicus ). Dorsal , the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction. IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions. Copyright © 2017 American Society for Microbiology.

Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels

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Amanda H. Lewis

2017-06-01

Full Text Available Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.

Phenotypic variation in dorsal fin morphology of coastal bottlenose dolphins (Tursiops truncatus off Mexico

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Eduardo Morteo

2017-06-01

Full Text Available Geographic variation in external morphology is thought to reflect an interplay between genotype and the environment. Morphological variation has been well-described for a number of cetacean species, including the bottlenose dolphin (Tursiops truncatus. In this study we analyzed dorsal fin morphometric variation in coastal bottlenose dolphins to search for geographic patterns at different spatial scales. A total of 533 dorsal fin images from 19 available photo-identification catalogs across the three Mexican oceanic regions (Pacific Ocean n = 6, Gulf of California n = 6 and, Gulf of Mexico n = 7 were used in the analysis. Eleven fin shape measurements were analyzed to evaluate fin polymorphism through multivariate tests. Principal Component Analysis on log-transformed standardized ratios explained 94% of the variance. Canonical Discriminant Function Analysis on factor scores showed separation among most study areas (p < 0.05 with exception of the Gulf of Mexico where a strong morphometric cline was found. Possible explanations for the observed differences are related to environmental, biological and evolutionary processes. Shape distinction between dorsal fins from the Pacific and those from the Gulf of California were consistent with previously reported differences in skull morphometrics and genetics. Although the functional advantages of dorsal fin shape remains to be assessed, it is not unlikely that over a wide range of environments, fin shape may represent a trade-off among thermoregulatory capacity, hydrodynamic performance and the swimming/hunting behavior of the species.

Descendant root volume varies as a function of root type: estimation of root biomass lost during uprooting in Pinus pinaster.

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Danjon, Frédéric; Caplan, Joshua S; Fortin, Mathieu; Meredieu, Céline

2013-01-01

Root systems of woody plants generally display a strong relationship between the cross-sectional area or cross-sectional diameter (CSD) of a root and the dry weight of biomass (DWd) or root volume (Vd) that has grown (i.e., is descendent) from a point. Specification of this relationship allows one to quantify root architectural patterns and estimate the amount of material lost when root systems are extracted from the soil. However, specifications of this relationship generally do not account for the fact that root systems are comprised of multiple types of roots. We assessed whether the relationship between CSD and Vd varies as a function of root type. Additionally, we sought to identify a more accurate and time-efficient method for estimating missing root volume than is currently available. We used a database that described the 3D root architecture of Pinus pinaster root systems (5, 12, or 19 years) from a stand in southwest France. We determined the relationship between CSD and Vd for 10,000 root segments from intact root branches. Models were specified that did and did not account for root type. The relationships were then applied to the diameters of 11,000 broken root ends to estimate the volume of missing roots. CSD was nearly linearly related to the square root of Vd, but the slope of the curve varied greatly as a function of root type. Sinkers and deep roots tapered rapidly, as they were limited by available soil depth. Distal shallow roots tapered gradually, as they were less limited spatially. We estimated that younger trees lost an average of 17% of root volume when excavated, while older trees lost 4%. Missing volumes were smallest in the central parts of root systems and largest in distal shallow roots. The slopes of the curves for each root type are synthetic parameters that account for differentiation due to genetics, soil properties, or mechanical stimuli. Accounting for this differentiation is critical to estimating root loss accurately.

Emotional detachment in psychopathy: Involvement of dorsal default-mode connections.

Science.gov (United States)

Sethi, Arjun; Gregory, Sarah; Dell'Acqua, Flavio; Periche Thomas, Eva; Simmons, Andy; Murphy, Declan G M; Hodgins, Sheilagh; Blackwood, Nigel J; Craig, Michael C

2015-01-01

Criminal psychopathy is defined by emotional detachment [Psychopathy Checklist - Revised (PCL-R) factor 1], and antisocial behaviour (PCL-R factor 2). Previous work has associated antisocial behaviour in psychopathy with abnormalities in a ventral temporo-amygdala-orbitofrontal network. However, little is known of the neural correlates of emotional detachment. Imaging studies have indicated that the 'default-mode network' (DMN), and in particular its dorsomedial (medial prefrontal - posterior cingulate) component, contributes to affective and social processing in healthy individuals. Furthermore, recent work suggests that this network may be implicated in psychopathy. However, no research has examined the relationship between psychopathy, emotional detachment, and the white matter underpinning the DMN. We therefore used diffusion tensor imaging (DTI) tractography in 13 offenders with psychopathy and 13 non-offenders to investigate the relationship between emotional detachment and the microstructure of white matter connections within the DMN. These included the dorsal cingulum (containing the medial prefrontal - posterior cingulate connections of the DMN), and the ventral cingulum (containing the posterior cingulate - medial temporal connections of the DMN). We found that fractional anisotropy (FA) was reduced in the left dorsal cingulum in the psychopathy group (p = .024). Moreover, within this group, emotional detachment was negatively correlated with FA in this tract portion bilaterally (left: r = -.61, p = .026; right: r = -.62, p = .023). These results suggest the importance of the dorsal DMN in the emotional detachment observed in individuals with psychopathy. We propose a 'dual-network' model of white matter abnormalities in the disorder, which incorporates these with previous findings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monitoring of glucose levels in mouse blood with noninvasive optical methods

International Nuclear Information System (INIS)

Ullah, H; Ikram, M; Ahmed, E

2014-01-01

We report the quantification/monitoring of glucose levels in a blood sample using optical diffuse reflectance (ODR) underlying variations in optical parameters with a white light source (at peak wavelength ∼600 nm and range 450–850 nm) and in blood in vivo using M-mode optical coherence tomography (OCT) in terms of the translational diffusion coefficient (D T ). In the ODR experiments, we have investigated two types of mono-dispersive particles, i.e. polystyrene microspheres (PMSs) with diameters of 1.4 μm (variable concentrations) and 2.6 μm (fixed concentration) in a water phantom by observing changes in the reduced scattering coefficient. We believe that these differences in optical properties will be helpful for the understanding and optimal use of laser applications in blood glucometry without piercing the skin. In the OCT experiments, this idea of glucose monitoring was applied on an in vivo normal mouse without injection of glucose intravenously to provide the threshold levels by envisioning/identifying a blood vessel by speckle variance (SV-OCT) using a dorsal skinfold mouse windows chamber model. We report an average value of translation decorrelation time τ T = 41.18 ± 1.92 ms and D T = 8.90 × 10 −14  m 2  s −1 underlying the dynamic light scattering (DLS). Our results have a potential application in the quantification of higher glucose levels in vivo administrated intravenously. (paper)

Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells.

Science.gov (United States)

Goto, So; Onishi, Akishi; Misaki, Kazuyo; Yonemura, Shigenobu; Sugita, Sunao; Ito, Hiromi; Ohigashi, Yoko; Ema, Masatsugu; Sakaguchi, Hirokazu; Nishida, Kohji; Takahashi, Masayo

2018-04-03

VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1 -/- mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1 -/- mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1 -/- pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1 -/- mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1 -/- choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion. © 2018, Goto et al.

[Case of surgical treatment for giant hemangioblastoma in the dorsal medulla oblongata].

Science.gov (United States)

Kamoshima, Yuuta; Terasaka, Shunsuke; Shimoda, Yusuke; Kobayashi, Hiroyuki; Kuroda, Satoshi; Asano, Takeshi; Yamaguchi, Shigeru; Murata, Junichi; Houkin, Kiyohiro

2012-03-01

Hemangioblastoma in the medulla oblongata is a relatively rare tumor. We present the case of a giant hemangioblastoma occurring in the dorsal medulla oblongata. A 33-year-old man with no neurological symptoms was diagnosed with a hemangioblastoma in the dorsal medulla oblongata, and opted for observation in the outpatient department. After 22 months of observation time, MRI scans showed rapid local tumor progression and obstructive hydrocephalus. At this point, he presented with mild dysphagia as a preoperative neurological deficit. Total surgical removal of the tumor was performed after temporary ventricle drainage and preoperative embolization of the feeding artery. Postoperatively, he became fully conscious but developed bulbar palsy followed by tracheostomy. During the 12 months of postoperative follow-up, severe dysphagia was still present.

Concurrent TMS-fMRI Reveals Interactions between Dorsal and Ventral Attentional Systems

DEFF Research Database (Denmark)

Leitao, Joana; Thielscher, Axel; Tuennerhoff, Johannes

2015-01-01

interactively in this process. This fMRI study used concurrent transcranial magnetic stimulation (TMS) as a causal perturbation approach to investigate the interactions between dorsal and ventral attentional systems and sensory processing areas. In a sustained spatial attention paradigm, human participants......Adaptive behavior relies on combining bottom-up sensory inputs with top-down control signals to guide responses in line with current goals and task demands. Over the past decade, accumulating evidence has suggested that the dorsal and ventral frontoparietal attentional systems are recruited......-TMS relative to Sham-TMS increased activation in the parietal cortex regardless of sensory stimulation, confirming the neural effectiveness of TMS stimulation. Visual targets increased activations in the anterior insula, a component of the ventral attentional system responsible for salience detection...

Characterizing pathways by which gravitropic effectors could move from the root cap to the root of primary roots of Zea mays

Science.gov (United States)

Moore, R.; McClelen, C. E.

1989-01-01

Plasmodesmata linking the root cap and root in primary roots Zea mays are restricted to approx. 400 protodermal cells bordering approx. 110000 microns2 of the calyptrogen of the root cap. This area is less than 10% of the cross-sectional area of the root-tip at the cap junction. Therefore, gravitropic effectors moving from the root cap to the root can move symplastically only through a relatively small area in the centre of the root. Decapped roots are non-responsive to gravity. However, decapped roots whose caps are replaced immediately after decapping are strongly graviresponsive. Thus, gravicurvature occurs only when the root cap contacts the root, and symplastic continuity between the cap and root is not required for gravicurvature. Completely removing mucilage from the root tip renders the root non-responsive to gravity. Taken together, these data suggest that gravitropic effectors move apoplastically through mucilage from the cap to the root.

Paresthesia thresholds in spinal cord stimulation: a comparison of theoretical results with clinical data

NARCIS (Netherlands)

Struijk, J.J.; Struijk, Johannes J.; Holsheimer, J.; Barolat, Giancarlo; He, Jiping; Boom, H.B.K.

1993-01-01

The potential distributions produced in the spinal cord and surrounding tissues by dorsal epidural stimulation at the midcervical, midthoracic, and low thoracic levels were calculated with the use of a volume conductor model. Stimulus thresholds of myelinated dorsal column fibers and dorsal root

Light and electron microscopy of contacts between primary afferent fibres and neurones with axons ascending the dorsal columns of the feline spinal cord.

Science.gov (United States)

Maxwell, D J; Koerber, H R; Bannatyne, B A

1985-10-01

In addition to primary afferent fibres, the dorsal columns of the cat spinal cord contain ascending second-order axons which project to the dorsal column nuclei. The aim of the present study was to obtain morphological evidence that certain primary afferent axons form monosynaptic contacts with cells of origin of this postsynaptic dorsal column pathway. In ten adult cats, neurones with axons ascending the dorsal columns were retrogradely labelled with horseradish peroxidase using a pellet implantation method in the thoracic dorsal columns. In the lumbosacral regions of the same animals, primary afferent fibres were labelled intra-axonally with ionophoretic application of horseradish peroxidase. Tissue containing labelled axons was prepared for light and combined light and electron microscopy. Ultrastructural examination demonstrated that slowly adapting (Type I), hair follicle, Pacinian corpuscle and group Ia muscle spindle afferents formed monosynaptic contacts with labelled cells and light microscopical analysis suggested that they also received monosynaptic input from rapidly adapting (Krause) afferents. This evidence suggests that sensory information from large-diameter cutaneous and muscle spindle afferent fibres is conveyed disynaptically via the postsynaptic dorsal column pathway to the dorsal column nuclei. Some of the input to this pathway is probably modified in the spinal cord as the majority of primary afferent boutons forming monosynaptic contacts were postsynaptic to other axon terminals. The postsynaptic dorsal column system appears to constitute a major somatosensory pathway in the cat.

Centralized mouse repositories.

Science.gov (United States)

Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

2012-10-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

Root anatomy, morphology, and longevity among root orders in Vaccinium corymbosum (Ericaceae).

Science.gov (United States)

Valenzuela-Estrada, Luis R; Vera-Caraballo, Vivianette; Ruth, Leah E; Eissenstat, David M

2008-12-01

Understanding root processes at the whole-plant or ecosystem scales requires an accounting of the range of functions within a root system. Studying root traits based on their branching order can be a powerful approach to understanding this complex system. The current study examined the highly branched root system of the ericoid plant, Vaccinium corymbosum L. (highbush blueberry) by classifying its root orders with a modified version of the morphometric approach similar to that used in hydrology for stream classification. Root anatomy provided valuable insight into variation in root function across orders. The more permanent portion of the root system occurred in 4th- and higher-order roots. Roots in these orders had radial growth; the lowest specific root length, N:C ratios, and mycorrhizal colonization; the highest tissue density and vessel number; and the coarsest root diameter. The ephemeral portion of the root system was mainly in the first three root orders. First- and 2nd-order roots were nearly anatomically identical, with similar mycorrhizal colonization and diameter, and also, despite being extremely fine, median lifespans were not very short (115-120 d; estimated with minirhizotrons). Our research underscores the value of examining root traits by root order and its implications to understanding belowground processes.

Anatomy of the dorsal default-mode network in conduct disorder: Association with callous-unemotional traits.

Science.gov (United States)

Sethi, Arjun; Sarkar, Sagari; Dell'Acqua, Flavio; Viding, Essi; Catani, Marco; Murphy, Declan G M; Craig, Michael C

2018-04-01

We recently reported that emotional detachment in adult psychopathy was associated with structural abnormalities in the dorsal 'default-mode' network (DMN). However, it is unclear whether these differences are present in young people at risk of psychopathy. The most widely recognised group at risk for psychopathy are children/adolescents with conduct disorder (CD) and callous-unemotional (CU) traits. We therefore examined the microstructure of the dorsal DMN in 27 CD youths (14-with/13-without CU traits) compared to 16 typically developing controls using DTI tractography. Both CD groups had significantly (p < 0.025) reduced dorsal DMN radial diffusivity compared to controls. In those with diagnostically significant CU traits, exploratory analyses (uncorrected for multiple comparisons) suggested that radial diffusivity was negatively correlated with CU severity (Left: rho = -0.68, p = 0.015). These results suggest that CD youths have microstructural abnormalities in the same network as adults with psychopathy. Further, the association with childhood/adolescent measures of emotional detachment (CU traits) resembles the relationship between emotional detachment and network microstructure in adult psychopaths. However, these changes appear to occur in opposite directions - with increased myelination in adolescent CD but reduced integrity in adult psychopathy. Collectively, these findings suggest that developmental abnormalities in dorsal DMN may play a role in the emergence of psychopathy. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A radiologic study on the urinary bladder following dorsal and ...

African Journals Online (AJOL)

Pneumocystography and positive contrast cystography using solutrast® were carried out immediately after surgery and on the second operative day following dorsal and ventral cystotomy in 22 adult mongrel dogs. In all the radiographs, there was no contrast observed in the abdominal cavity and the apex of the bladder had ...

Abnormal global processing along the dorsal visual pathway in autism: a possible mechanism for weak visuospatial coherence?

Science.gov (United States)

Pellicano, Elizabeth; Gibson, Lisa; Maybery, Murray; Durkin, Kevin; Badcock, David R

2005-01-01

Frith and Happe (Frith, U., & Happe, F. (1994). Autism: Beyond theory of mind. Cognition, 50, 115-132) argue that individuals with autism exhibit 'weak central coherence': an inability to integrate elements of information into coherent wholes. Some authors have speculated that a high-level impairment might be present in the dorsal visual pathway in autism, and furthermore, that this might account for weak central coherence, at least at the visuospatial level. We assessed the integrity of the dorsal visual pathway in children diagnosed with an autism spectrum disorder (ASD), and in typically developing children, using two visual tasks, one examining functioning at higher levels of the dorsal cortical stream (Global Dot Motion (GDM)), and the other assessing lower-level dorsal stream functioning (Flicker Contrast Sensitivity (FCS)). Central coherence was tested using the Children's Embedded Figures Test (CEFT). Relative to the typically developing children, the children with ASD had shorter CEFT latencies and higher GDM thresholds but equivalent FCS thresholds. Additionally, CEFT latencies were inversely related to GDM thresholds in the ASD group. These outcomes indicate that the elevated global motion thresholds in autism are the result of high-level impairments in dorsal cortical regions. Weak visuospatial coherence in autism may be in the form of abnormal cooperative mechanisms in extra-striate cortical areas, which might contribute to differential performance when processing stimuli as Gestalts, including both dynamic (i.e., global motion perception) and static (i.e., disembedding performance) stimuli.

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

Science.gov (United States)

McDonald, Robert J; Jones, Jana; Richards, Blake; Hong, Nancy S

2006-09-01

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

A preliminary study of the sensory distribution of the penile dorsal and ventral nerves: implications for effective penile block for circumcision.

LENUS (Irish Health Repository)

Long, Ronan M

2012-01-31

OBJECTIVE: To determine the sensory innervation of the penis, as regional anaesthesia is often used either for postoperative analgesia or as the sole anaesthetic technique for circumcision. Since first described in 1978 the dorsal penile nerve block has become the standard technique, but some blocks are ineffective; a better understanding of the sensory innervation of the penis might improve the efficacy of the dorsal penile block technique. PATIENTS AND METHODS: In 13 men undergoing circumcision with local anaesthetic, cutaneous sensation was tested before and after infiltration of the dorsal aspect of the penis, and then again after infiltration of the ventral aspect. The area of anaesthesia was mapped using pin-prick sensation. RESULTS: Ten of the 13 patients showed a similar pattern of sensory distribution. After the dorsal block, the dorsal aspect of the shaft of the penis and glans penis became insensate. The ventral aspect of the shaft remained sensate up to and including the frenulum. After successful ventral infiltration all sensate areas became insensate and circumcision proceeded. In one case the frenulum and distal ventral foreskin was anaesthetized after the dorsal block and ventral infiltration was not required. No patient experienced pain during circumcision. CONCLUSION: For consistently successful regional anaesthesia of the foreskin in circumcision, a dorsal block must be used. This should be combined with ventral infiltration at the site of incision. This method will avoid inconsistencies and allow pain-free circumcision using local anaesthesia in most men.

SCANNING ELECTRON MICROSCOPY STUDY OF THE DORSAL SURFACE OF THE TONGUE IN Chaetophractus vellerosus (MAMMALIA, DASYPODIDAE)

OpenAIRE

Estecondo, Silvia; Codón, Stella Maris; Casanave, Emma Beatriz

2001-01-01

The characteristics of the dorsal surface of Chaetophractus vellerosus tongue were studied by scanning electron microscopy. Simple or branched filiform, fungiform and vallate papillae are described. Simple conical filiform papillae appear in the apex, lateral edges and posterior third, caudally to the circumvallated ones. The branched papillae are densely distributed all over the dorsal surface of the lingual body. Fungiform ones are scattered among the branched filiform papillae. In the post...

Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

Energy Technology Data Exchange (ETDEWEB)

Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan); Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan)

2009-10-30

The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

International Nuclear Information System (INIS)

Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

2009-01-01

The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li 2 CO 3 were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

OpenAIRE

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon; Chung, Jin Mo

2011-01-01

Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in res...

OpenSimRoot: widening the scope and application of root architectural models.

Science.gov (United States)

Postma, Johannes A; Kuppe, Christian; Owen, Markus R; Mellor, Nathan; Griffiths, Marcus; Bennett, Malcolm J; Lynch, Jonathan P; Watt, Michelle

2017-08-01

OpenSimRoot is an open-source, functional-structural plant model and mathematical description of root growth and function. We describe OpenSimRoot and its functionality to broaden the benefits of root modeling to the plant science community. OpenSimRoot is an extended version of SimRoot, established to simulate root system architecture, nutrient acquisition and plant growth. OpenSimRoot has a plugin, modular infrastructure, coupling single plant and crop stands to soil nutrient and water transport models. It estimates the value of root traits for water and nutrient acquisition in environments and plant species. The flexible OpenSimRoot design allows upscaling from root anatomy to plant community to estimate the following: resource costs of developmental and anatomical traits; trait synergisms; and (interspecies) root competition. OpenSimRoot can model three-dimensional images from magnetic resonance imaging (MRI) and X-ray computed tomography (CT) of roots in soil. New modules include: soil water-dependent water uptake and xylem flow; tiller formation; evapotranspiration; simultaneous simulation of mobile solutes; mesh refinement; and root growth plasticity. OpenSimRoot integrates plant phenotypic data with environmental metadata to support experimental designs and to gain a mechanistic understanding at system scales. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

Science.gov (United States)

Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

The brain's dorsal route for speech represents word meaning: evidence from gesture.

Science.gov (United States)

Josse, Goulven; Joseph, Sabine; Bertasi, Eric; Giraud, Anne-Lise

2012-01-01

The dual-route model of speech processing includes a dorsal stream that maps auditory to motor features at the sublexical level rather than at the lexico-semantic level. However, the literature on gesture is an invitation to revise this model because it suggests that the premotor cortex of the dorsal route is a major site of lexico-semantic interaction. Here we investigated lexico-semantic mapping using word-gesture pairs that were either congruent or incongruent. Using fMRI-adaptation in 28 subjects, we found that temporo-parietal and premotor activity during auditory processing of single action words was modulated by the prior audiovisual context in which the words had been repeated. The BOLD signal was suppressed following repetition of the auditory word alone, and further suppressed following repetition of the word accompanied by a congruent gesture (e.g. ["grasp" + grasping gesture]). Conversely, repetition suppression was not observed when the same action word was accompanied by an incongruent gesture (e.g. ["grasp" + sprinkle]). We propose a simple model to explain these results: auditory and visual information converge onto premotor cortex where it is represented in a comparable format to determine (in)congruence between speech and gesture. This ability of the dorsal route to detect audiovisual semantic (in)congruence suggests that its function is not restricted to the sublexical level.

Light as stress factor to plant roots - case of root halotropism.

Science.gov (United States)

Yokawa, Ken; Fasano, Rossella; Kagenishi, Tomoko; Baluška, František

2014-01-01

Despite growing underground, largely in darkness, roots emerge to be very sensitive to light. Recently, several important papers have been published which reveal that plant roots not only express all known light receptors but also that their growth, physiology and adaptive stress responses are light-sensitive. In Arabidopsis, illumination of roots speeds-up root growth via reactive oxygen species-mediated and F-actin dependent process. On the other hand, keeping Arabidopsis roots in darkness alters F-actin distribution, polar localization of PIN proteins as well as polar transport of auxin. Several signaling components activated by phytohormones are overlapping with light-related signaling cascade. We demonstrated that the sensitivity of roots to salinity is altered in the light-grown Arabidopsis roots. Particularly, light-exposed roots are less effective in their salt-avoidance behavior known as root halotropism. Here we discuss these new aspects of light-mediated root behavior from cellular, physiological and evolutionary perspectives.

Selective Entrainment of Theta Oscillations in the Dorsal Stream Causally Enhances Auditory Working Memory Performance.

Science.gov (United States)

Albouy, Philippe; Weiss, Aurélien; Baillet, Sylvain; Zatorre, Robert J

2017-04-05

The implication of the dorsal stream in manipulating auditory information in working memory has been recently established. However, the oscillatory dynamics within this network and its causal relationship with behavior remain undefined. Using simultaneous MEG/EEG, we show that theta oscillations in the dorsal stream predict participants' manipulation abilities during memory retention in a task requiring the comparison of two patterns differing in temporal order. We investigated the causal relationship between brain oscillations and behavior by applying theta-rhythmic TMS combined with EEG over the MEG-identified target (left intraparietal sulcus) during the silent interval between the two stimuli. Rhythmic TMS entrained theta oscillation and boosted participants' accuracy. TMS-induced oscillatory entrainment scaled with behavioral enhancement, and both gains varied with participants' baseline abilities. These effects were not seen for a melody-comparison control task and were not observed for arrhythmic TMS. These data establish theta activity in the dorsal stream as causally related to memory manipulation. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

effects of different concentrations of auxins on rooting and root

African Journals Online (AJOL)

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ABSTRACT: The effect of auxins and their different concentrations on rooting and root ... primary root length and the longest primary root was recorded with the ... ceuticals, lubricants, foods, electrical insulators, .... stem cuttings of jojoba treated with IBA and NAA, .... increasing cell division and enlargement at each.