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Sample records for striatum substantia nigra

  1. The aberrantly expressed long non-coding RNA in the substantia nigra and corpus striatum of Nrf2-knockout mice.

    Science.gov (United States)

    Liu, Jian; Xu, Yali; Kang, Yunxiao; Cao, Shanhu; Shi, Geming; Cui, Huixian; Sun, Shaoguang; Wang, Lei

    2017-10-01

    Nuclear factor erythroid 2 like 2 (Nrf2) functions as a neuroprotective agent in Parkinson's disease (PD). This study aimed to investigate the key long non-coding RNAs (lncRNAs) correlated with Nrf2, which might provide valuable information for the exploration of pathogenesis of PD. The lncRNA and mRNA expression profiling of substantia nigra and corpus striatum of Nrf2 (-/-) mice model was obtained from microarray analysis. The animal experiments conducted for this study were approved by the ethics committee of Hebei Medical University. Bioinformatics analyses were conducted, including differentially expressed lncRNAs/mRNA (differentially expressed lncRNA, DEL/differentially expressed mRNA, DEM) identification, DEL-DEM coexpression network construction, and biological functions prediction. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate abnormally expressed DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice model. A total of 48 DELs (37 down-regulated and 11 up-regulated) were identified both in Nrf2 (-/-) substantia nigra and corpus striatum; 96 DEMs and 643 DEMs were identified in the substantia nigra and corpus striatum, respectively. DEL-DEM coexpressed network was constructed. LncRNA AK076880, AK036620, and AK020330 had high connectivity with DEMs both in the substantia nigra and corpus striatum. These DEMs were significantly enriched in signaling pathways such as the calcium signaling pathway, Huntington's disease, Alzheimer's disease, mitogen-activated protein kinase (MAPK) signaling pathway, and the Wnt signaling pathway. Generally, qRT-PCR validation results of selected DEMs and DELs were consistent with microarray data. The dysregulated DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice were identified. Our results might provide useful information for further exploring the pathogenesis mechanism of PD. © 2017 International Society for Neurochemistry.

  2. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model.

    Science.gov (United States)

    Lu, Yi; Zhang, Xiaoxia; Zhao, Liangcai; Yang, Changwei; Pan, Linlin; Li, Chen; Liu, Kun; Bai, Guanghui; Gao, Hongchang; Yan, Zhihan

    2018-01-01

    Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD), while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo 1 H nuclear magnetic resonance (NMR) spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN) of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu) in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA) increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI) and taurine (Tau) were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

  3. Light pigmentation phenotype is correlated with increased substantia nigra echogenicity.

    Science.gov (United States)

    Rumpf, Jost-Julian; Schirmer, Maria; Fricke, Christopher; Weise, David; Wagner, Justinus Aspasios; Simon, Jan; Classen, Joseph

    2015-11-01

    This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinson's disease. In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects. Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning. Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society.

  4. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

    Science.gov (United States)

    Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

    2018-02-01

    Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known

  5. AAV Vector-Mediated Gene Delivery to Substantia Nigra Dopamine Neurons: Implications for Gene Therapy and Disease Models

    Directory of Open Access Journals (Sweden)

    Katrina Albert

    2017-02-01

    Full Text Available Gene delivery using adeno-associated virus (AAV vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson′s disease. AAV-based gene targeting to the projection area of these neurons in the striatum has been studied extensively to induce the production of neurotrophic factors for disease-modifying therapies for Parkinson′s disease. Much less emphasis has been put on AAV-based gene therapy targeting dopamine neurons in substantia nigra. We will review the literature related to targeting striatum and/or substantia nigra dopamine neurons using AAVs in order to express neuroprotective and neurorestorative molecules, as well as produce animal disease models of Parkinson′s disease. We discuss difficulties in targeting substantia nigra dopamine neurons and their vulnerability to stress in general. Therefore, choosing a proper control for experimental work is not trivial. Since the axons along the nigrostriatal tract are the first to degenerate in Parkinson′s disease, the location to deliver the therapy must be carefully considered. We also review studies using AAV-a-synuclein (a-syn to target substantia nigra dopamine neurons to produce an α-syn overexpression disease model in rats. Though these studies are able to produce mild dopamine system degeneration in the striatum and substantia nigra and some behavioural effects, there are studies pointing to the toxicity of AAV-carrying green fluorescent protein (GFP, which is often used as a control. Therefore, we discuss the potential difficulties in overexpressing proteins in general in

  6. Distinct cellular and molecular environments support aging-related DNA methylation changes in the substantia nigra.

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    Fasolino, Maria; Liu, Shuo; Wang, Yinsheng; Zhou, Zhaolan

    2017-01-01

    We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments. We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice. The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons. Additionally, this age-dependent alteration in methylation correlates with a reduction in the ratio of α-ketoglutarate to succinate in the SN. Distinct cellular and molecular environments correlate with aging-associated methylation changes in the SN, implicating this epigenetic mechanism in the susceptibility of this brain region to age-related cell loss.

  7. Assessment of substantia nigra echogenicity in German and Filipino populations using a portable ultrasound system.

    Science.gov (United States)

    Go, Criscely L; Frenzel, Antonia; Rosales, Raymond L; Lee, Lillian V; Benecke, Reiner; Dressler, Dirk; Walter, Uwe

    2012-02-01

    Transcranial sonography of the substantia nigra for diagnosing premotor stages of Parkinson disease has been attracting increasing interest. Standard reference values defining an abnormal increased echogenic size (hyperechogenicity) of the substantia nigra have been established in several populations using high-end stationary ultrasound systems. It is unknown whether a portable ultrasound system can be appropriately used and how the Filipino population would compare with the well-studied white population. We prospectively studied substantia nigra echogenic sizes and third ventricle widths in 71 healthy adult German participants and 30 age- and sex-matched Filipino participants using both a well-established stationary ultrasound system (in the German cohort) and a recently distributed portable ultrasound system (in both ethnic cohorts). Mean substantia nigra echogenic sizes, cutoff values defining abnormal hyperechogenicity, and intra-rater reliability were similar with both systems and in both ethnic cohorts studied. The Filipino and German participants did not differ with respect to the frequency of insufficient insonation conditions (each 3%) and substantia nigra hyperechogenicity (10% versus 9%; P = .80). However, third ventricle widths were smaller in the Filipino than the German participants (mean ± SD, 1.6 ± 1.1 versus 2.4 ± 1.0 mm; P = .004). The frequency of substantia nigra hyperechogenicity appears to be homogeneous in white and Asian populations. Screening for this feature may well be performed with a present-day portable ultrasound system.

  8. [18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP.

    Science.gov (United States)

    Coakeley, Sarah; Cho, Sang Soo; Koshimori, Yuko; Rusjan, Pablo; Ghadery, Christine; Kim, Jinhee; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2018-03-01

    This study investigated binding of [ 18 F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). [ 18 F]AV-1451 is a positron emission tomography radiotracer designed to bind pathological tau. A post-mortem study using [ 18 F]AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra. A subsequent clinical study reported a 30% decrease in [ 18 F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited. An anatomical MRI and a 90-min PET scan, using [ 18 F]AV-1451, were acquired from all participants. The standardized uptake value ratio (SUVR) from 60 to 90 min post-injection was calculated for the substantia nigra, using the cerebellar cortex as the reference region. The substantia nigra was delineated using automated region of interest software. An independent samples ANOVA and LSD post hoc testing were used to test for differences in [ 18 F]AV-1451 SUVR between groups. Substantia nigra SUVR from 60 to 90 min was significantly greater in HC compared to both PSP and PD groups. Although the PD group had the lowest SUVR, there was no significant difference in substantia nigra uptake between PD and PSP. [ 18 F]AV-1451 may be the first PET radiotracer capable of imaging neurodegeneration of the substantia nigra in parkinsonisms. Further testing must be done in PD and atypical parkinsonian disorders to support this off-target use of [ 18 F]AV-1451.

  9. Age and Parkinson's disease-related neuronal death in the substantia nigra pars compacta

    DEFF Research Database (Denmark)

    Eriksen, Nina; Stark, Anette Kirstine; Pakkenberg, Bente

    2009-01-01

    of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed......During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder...

  10. Electrophysiological localization of distinct calcium potentials at selective somatodendritic sites in the substantia nigra

    DEFF Research Database (Denmark)

    Hounsgaard, J; Nedergaard, S; Greenfield, S A

    1992-01-01

    of differential polarization through applied electric fields, the cell body and dendrites have been activated in effective isolation during intracellular recordings from pars compacta neurons in the substantia nigra in vitro. In one class of neurons, which discharge in a "phasic" fashion and are located...... in the rostral substantia nigra, the dendrites are shown to be the origin of classic low-threshold and high-threshold type calcium potentials: indeed the high-threshold conductance appears to be exclusively dendritic. By contrast, in a second, more caudally located cell type, which discharges rhythmically...

  11. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease

    International Nuclear Information System (INIS)

    Kamagata, Koji; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K.; Aoki, Shigeki; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Hattori, Nobutaka; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei

    2016-01-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P < 0.00058). Vic and OD in the SNpc and putamen showed significant negative correlations (P < 0.05) with disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. (orig.)

  12. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease.

    Science.gov (United States)

    Kamagata, Koji; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K; Hattori, Nobutaka; Aoki, Shigeki

    2016-08-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. • Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique • NODDI estimates neurite microstructure more specifically than diffusion tensor imaging • By using NODDI, nigrostriatal alterations in PD can be evaluated in vivo • NOODI is useful for diagnosing PD and assessing its disease progression.

  13. Stimulation of the substantia nigra influences the specification of memory-guided saccades

    OpenAIRE

    Mahamed, Safraaz; Garrison, Tiffany J.; Shires, Joel; Basso, Michele A.

    2013-01-01

    In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activi...

  14. Substantia nigra in MR images in Parkinson disease and MPTP exposure

    International Nuclear Information System (INIS)

    De La Paz, R.L.; Duguid, J.; Langston, W.J.

    1986-01-01

    Eight patients, aged 60-77 years, with idiopathic Parkinson disease were studied to determine whether the characteristic degeneration of the substantia nigra (zona compacta), seen pathologically, could be identified in vivo on T2-weighted proton MR imaging (1.5 T). The mean width of the substantia nigra in the eight patients was 4.1 mm (SEM = 0.21 mm), significantly (rho < .004) less than the mean width of 5.2 mm (SEM= 0.30 mm) in ten age-matched controls. Overlap with control values was seen in only one patient. No clear correlation between low signal in the putamen (suggesting excess deposition of iron, Fe/sup 3+/) and Parkinson disease was seen. Narrowing of the substantia nigra on MR imaging was also seen in one patient with drug-induced Parkinson syndrome (MPTP exposure). These changes on MR imaging are probably due to atrophy of the zona compacta of the substantia nigra, but excess iron in the zona reticulata may partially contribute to these findings. MR imaging may be useful for differentiating ''classic'' Parkinson disease from other extrapyramidal degenerative disorders and for predicting response to drug therapy

  15. Ventral Tegmental Area and Substantia Nigra Neural Correlates of Spatial Learning

    Science.gov (United States)

    Martig, Adria K.; Mizumori, Sheri J. Y.

    2011-01-01

    The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) may provide modulatory signals that, respectively, influence hippocampal (HPC)- and striatal-dependent memory. Electrophysiological studies investigating neural correlates of learning and memory of dopamine (DA) neurons during classical conditioning tasks have found DA…

  16. CHARACTERIZATION OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA-RETICULATA BY MEANS OF BRAIN MICRODIALYSIS

    NARCIS (Netherlands)

    TIMMERMAN, W; ZWAVELING, J; WESTERINK, BHC

    Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4-8 h after surgery; day 1) and chronically implanted probes

  17. Age and Parkinson's disease-related neuronal death in the substantia nigra pars compacta

    DEFF Research Database (Denmark)

    Eriksen, Nina; Stark, Anette Kirstine; Pakkenberg, Bente

    2009-01-01

    During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder of this s......During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder...... of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed...

  18. 9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease

    Directory of Open Access Journals (Sweden)

    LA Massey

    2017-01-01

    Conclusions: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.

  19. Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced substantia nigra lesion in rats.

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    Haghparast, Elham; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Sheibani, Vahid

    2018-04-01

    Although Parkinson's disease (PD) is well known with its motor deficits, the patients often suffer from cognitive dysfunction. Apelin, as the endogenous ligand of the APJ receptor, is found in several brain regions such as substantia nigra and mesolimbic pathway. However, the role of apelin in cognition and cognitive disorders has not been fully clarified. In this study the effects of apelin-13 were investigated on cognitive disorders in rat Parkinsonism experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the substantia nigra. Apelin-13 (1, 2 and 3μg/rat) was administered into the substantia nigra one week after the 6-OHDA injection. Morris water maze (MWM), object location and novel object recognition tests were performed one month after the apelin injection. 6-OHDA-treated animals showed a significant impairment in cognitive functions which was revealed by the increased in the escape latency and traveled distance in MWM test and decreased in the exploration index in novel object recognition and object location tasks. Apelin-13 (3μg/rat) significantly attenuates the mentioned cognitive impairments in 6-OHDA-treated animals. In conclusion, the data support the pro-cognitive property of apelin-13 in 6-OHDA-induced cognitive deficit and provided a new pharmacological aspect of the neuropeptide apelin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Chronic pramipexole treatment induces compulsive behavior in rats with 6-OHDA lesions of the substantia nigra and ventral tegmental area.

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    Dardou, D; Reyrolle, L; Chassain, C; Durif, F

    2017-08-14

    Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions. Accordingly, we aimed to mimic chronic DRT in a PD context, and obtain data on the brain regions that potentially sustain this type of compulsive behavior pattern in rats. We observed that the lesion or treatment alone did not induce compulsive lever pressing in rats. However, rats with lesions of the substantia nigra and ventral tegmental area as well as with chronic PPX treatment developed strong compulsive lever-pressing behavior, as measured via PTSA. Furthermore, when chronic PPX treatment was discontinued before the PTSA test, the lesioned rats showed the same level of compulsive behavior as sham-operated rats. In fact, lesioned, treated, and compulsive-like rats showed significantly higher Fos expression in the orbitofrontal cortex and dorsal striatum. Thus, chronic PPX treatment in PD rats induced a strong compulsive-like behavior. Furthermore, Fos expression mapping suggests that the behavior was sustained via the activation of the orbitofrontal cortex and dorsal striatum. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Hyperechogenicity of substantia nigra for differential diagnosis of Parkinson's disease: A meta-analysis.

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    Shafieesabet, Azin; Fereshtehnejad, Seyed-Mohammad; Shafieesabet, Azadeh; Delbari, Ahmad; Baradaran, Hamid Reza; Postuma, Ronald B; Lökk, Johan

    2017-09-01

    Studies have suggested that the majority of patients with Parkinson's disease have abnormal ultrasound hyperechogenicity of the substantia nigra, and that this may be useful in diagnosis. We performed a systematic review and meta-analysis to evaluate diagnostic value of substantia nigra ultrasound to differentiate Parkinson's disease from atypical parkinsonism and from essential tremor. We systematically searched PubMed and EMBASE for relevant studies published until November 2016. Eligible articles were screened, data were extracted and study quality was scored by two independent reviewers. We applied random effect models to calculate pooled estimates for the prevalence of hyperechogenicity in each condition. For final meta-analysis, 71 articles with a total number of 5730 participants (idiopathic Parkinson's disease: 4494, atypical parkinsonism: 594, essential tremor: 642) were included. The pooled prevalence rate of hyperechogenicity was 84% (95 %CI 80-87%) in idiopathic Parkinson's disease, 28% (95% CI 20-36%) in atypical parkinsonism and 15% (95% CI 7-23%) in essential tremor. Based on our meta-analysis, substantia nigra hyperechogenecity has 75% (95% CI: 60-86%) sensitivity and 70% (95% CI: 55-81%) specificity to differentiate idiopathic Parkinson's disease from atypical parkinsonism. Sensitivity and specificity to distinguish idiopathic Parkinson's disease from essential tremor was calculated as 78% (95% CI: 69-85%) and 85% (95% CI: 77-91%), respectively. Findings from our meta-analysis showed that transcranial sonography can provide useful information to differentiate idiopathic Parkinson's disease from mimicking movement disorders, although sensitivity and specificity are suboptimal, particularly for differentiating from atypical parkinsonism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra

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    Jian-qing Liang

    2016-01-01

    Full Text Available Tyrosine hydroxylase is a key enzyme in dopamine biosynthesis. Change in tyrosine hydroxylase expression in the nigrostriatal system is closely related to the occurrence and development of Parkinson′s disease. Verbascoside, an extract from Radix Rehmanniae Praeparata has been shown to be clinically effective in treating Parkinson′s disease. However, the underlying mechanisms remain unclear. It is hypothesized that the effects of verbascoside on Parkinson′s disease are related to tyrosine hydroxylase expression change in the nigrostriatal system. Rat models of Parkinson′s disease were established and verbascoside (60 mg/kg was administered intraperitoneally once a day. After 6 weeks of verbascoside treatment, rat rotational behavior was alleviated; tyrosine hydroxylase mRNA and protein expression and the number of tyrosine hydroxylase-immunoreactive neurons in the rat right substantia nigra were significantly higher than the Parkinson′s model group. These findings suggest that the mechanism by which verbascoside treats Parkinson′s disease is related to the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra.

  3. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

    Directory of Open Access Journals (Sweden)

    Alison L McCormack

    Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

  4. Human substantia nigra and ventral tegmental area involvement in computing social error signals during the ultimatum game.

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    Hétu, Sébastien; Luo, Yi; D'Ardenne, Kimberlee; Lohrenz, Terry; Montague, P Read

    2017-12-01

    As models of shared expectations, social norms play an essential role in our societies. Since our social environment is changing constantly, our internal models of it also need to change. In humans, there is mounting evidence that neural structures such as the insula and the ventral striatum are involved in detecting norm violation and updating internal models. However, because of methodological challenges, little is known about the possible involvement of midbrain structures in detecting norm violation and updating internal models of our norms. Here, we used high-resolution cardiac-gated functional magnetic resonance imaging and a norm adaptation paradigm in healthy adults to investigate the role of the substantia nigra/ventral tegmental area (SN/VTA) complex in tracking signals related to norm violation that can be used to update internal norms. We show that the SN/VTA codes for the norm's variance prediction error (PE) and norm PE with spatially distinct regions coding for negative and positive norm PE. These results point to a common role played by the SN/VTA complex in supporting both simple reward-based and social decision making. © The Author (2017). Published by Oxford University Press.

  5. Stimulation of the substantia nigra influences the specification of memory-guided saccades

    Science.gov (United States)

    Mahamed, Safraaz; Garrison, Tiffany J.; Shires, Joel

    2013-01-01

    In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects

  6. Stimulation of the substantia nigra influences the specification of memory-guided saccades.

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    Mahamed, Safraaz; Garrison, Tiffany J; Shires, Joel; Basso, Michele A

    2014-02-01

    In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects

  7. Oxidative stress-dependent changes in immune responses and cell death in the substantia nigra after ozone exposure in rat

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    Rivas-Arancibia, Selva; Zimbrón, Luis Fernando Hernández; Rodríguez-Martínez, Erika; Maldonado, Perla D.; Borgonio Pérez, Gabino; Sepúlveda-Parada, María

    2015-01-01

    Parkinson's disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control) or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent (1) spectrophotometric analysis for protein oxidation; (2) western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and (3) immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB, and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson's disease. PMID:25999851

  8. Protective Effects of Vitamin E Consumption against 3MT Electromagnetic Field Effects on Oxidative Parameters in Substantia Nigra in Rats

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    Ahmad Ali Ghanbari

    2016-10-01

    Conclusion: We demonstrated two important findings; that 50 days exposure to 3 MT electromagnetic field caused oxidative stress by increasing the levels of MDA, and decreasing SOD activity in the substantia nigra; and that treatment with the vitamin E significantly prevented the oxidative stress and lipid peroxidation.

  9. THE SIGNIFICANCE OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA OF THE RAT DURING SEIZURES AND ANTICONVULSANT TREATMENTS

    NARCIS (Netherlands)

    SAYIN, U; TIMMERMAN, W; WESTERINK, BHC

    1995-01-01

    The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold

  10. Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Groeger, Adriane; Godau, Jana; Berg, Daniela; Chadzynski, Grzegorz; Klose, Uwe

    2011-01-01

    To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252 ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls. (orig.)

  11. Quantifying iron deposition within the substantia nigra of Parkinson's disease by quantitative susceptibility mapping.

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    An, Hedi; Zeng, Xiaoyan; Niu, Tengfei; Li, Gaiying; Yang, Jie; Zheng, Lanlan; Zhou, Wei; Liu, Hong; Zhang, Miaomiao; Huang, Dongya; Li, Jianqi

    2018-03-15

    Iron deposition within the substantia nigra (SN) has been postulated to play a vital role in Parkinson's disease (PD). The aim of this study was to explore the inherent link of PD patients between their substantia nigra iron accumulation and clinical status using quantitative susceptibility mapping (QSM) which is now considered to be the only quantitative imaging technique of brain iron deposition. 44 PD patients and 31 age- and gender-matched healthy controls underwent quantitative susceptibility mapping (QSM) were recruited in this study. We firstly divided the patients into mild symptom severity (MSP) and advanced symptom severity (ASP) groups concerning their disease stage, aiming to illuminate the relationship between iron deposition in SN of PD and disease progression. Then, we classified the patients with Parkinson's disease into three subgroups: tremor-dominant PD (TD), akinetic/rigidity-dominant PD (AR), mixed-PD (M) according to their dominant motor symptoms in order to investigate whether there are any effects of SN iron accumulation to different subtypes of PD patients. Compared to healthy controls, patients with PD have increased QSM magnetic values in the substantia nigra (138.039±37.320 vs 179.553±65.715; P=0.001). More prominent statistically significance of the difference of SN iron deposition between healthy controls (HC) and advanced symptom severity (ASP) subgroup was displayed (138.039±37.320 vs 232.827±92.040; Pdifference compared with healthy controls concerning the QSM values (138.039±37.320 vs 185.864±99.851; P=0.013; 188.148±52.958 vs 138.039±37.320; P=0.001). Furthermore, the iron content in the SN of PD patients was significantly correlated with the Hoehn-Yahr stage, the Unified Parkinson's Disease Rating Scale (UPDRS), Montgomery Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) scores (r=0.417, P=0.005; r=0.300, P=0.048; r=0.540, P<0.001; r=0.553, P<0.001). In MSP the significantly correlation was

  12. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

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    Kyle Farmer

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA, or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0 and LPC (18:1, which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.

  13. Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.

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    Ghazaleh Samoudi

    Full Text Available BACKGROUND: The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA hemilesion model of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the γ-amino buturic acid (GABA transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN, the striatum or the ventromedial thalamus (VM. Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN. CONCLUSIONS/SIGNIFICANCE: SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for

  14. Dopamine reduction in the substantia nigra of Parkinson's disease patients confirmed by in vivo magnetic resonance spectroscopic imaging.

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    Adriane Gröger

    Full Text Available OBJECTIVES: Metabolic changes in the substantia nigra of patients with Parkinson's disease were previously investigated in different molecular-pathological examinations. The aim of our study was the in vivo measurement of these alterations using three-dimensional magnetic resonance spectroscopic imaging. METHODS: 21 patients with Parkinson's disease and 24 controls were examined using magnetic resonance spectroscopic imaging at 3 Tesla. The spectra of rostral and caudal substantia nigra regions were analyzed using LCModel. For spectral fitting, an adjusted basis data set with pathology-specific metabolites and macromolecules was used to better reproduce the in vivo spectra. To assess differences between both groups more accurately, especially in metabolites at lower concentrations, group-averaged spectra were evaluated in addition to the analysis of individual data. RESULTS: We found significantly decreased N-acetylaspartate, choline, creatine, myo-inositol, glutathione and dopamine concentrations in patients with Parkinson's disease compared to controls, whereas glutamine+glutamate, γ-aminobutyric acid, and homovanillic acid were slightly increased. According to anatomical features, clear differences in the biochemical profiles were found between rostral and caudal substantia nigra voxels in both groups. CONCLUSIONS: Reduced N-acetylaspartate and dopamine concentrations result from progressive degeneration of dopamine-producing neurons within the substantia nigra pars compacta. Decreased creatine levels can be interpreted as impaired energy metabolism due to mitochondrial dysfunction. Lower glutathione concentrations might be a cause or consequence of oxidative stress. Furthermore, slightly increased glutamine+glutamate and γ-aminobutyric acid levels are expected based on post mortem data in Parkinson's disease. To the best of our knowledge, this is the first non-invasive confirmation of these metabolic changes.

  15. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation.

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    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Rabelo, Thallita Kelly; Kunzler, Alice; Souza, Natália Cabral; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-08-18

    The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 μg per rat), injected concomitantly with 6-OHDA (10 μg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.

  16. Controlling absence seizures by deep brain stimulus applied on substantia nigra pars reticulata and cortex

    International Nuclear Information System (INIS)

    Hu, Bing; Wang, Qingyun

    2015-01-01

    Epilepsy is a typical neural disease in nervous system, and the control of seizures is very important for treating the epilepsy. It is well known that the drug treatment is the main strategy for controlling the epilepsy. However, there are about 10–15 percent of patients, whose seizures cannot be effectively controlled by means of the drug. Alternatively, the deep brain stimulus (DBS) technology is a feasible method to control the serious seizures. However, theoretical explorations of DBS are still absent, and need to be further made. Presently, we will explore to control the absence seizures by introducing the DBS to a basal ganglia thalamocortical network model. In particular, we apply DBS onto substantia nigra pars reticulata (SNr) and the cortex to explore its effects on controlling absence seizures, respectively. We can find that the absence seizure can be well controlled within suitable parameter ranges by tuning the period and duration of current stimulation as DBS is implemented in the SNr. And also, as the DBS is applied onto the cortex, it is shown that for the ranges of present parameters, only adjusting the duration of current stimulation is an effective control method for the absence seizures. The obtained results can have better understanding for the mechanism of DBS in the medical treatment.

  17. Operant self-stimulation of dopamine neurons in the substantia nigra.

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    Mark A Rossi

    Full Text Available We examined the contribution of the nigrostriatal DA system to instrumental learning and behavior using optogenetics in awake, behaving mice. Using Cre-inducible channelrhodopsin-2 (ChR2 in mice expressing Cre recombinase driven by the tyrosine hydroxylase promoter (Th-Cre, we tested whether selective stimulation of DA neurons in the substantia nigra pars compacta (SNC, in the absence of any natural rewards, was sufficient to promote instrumental learning in naive mice. Mice expressing ChR2 in SNC DA neurons readily learned to press a lever to receive laser stimulation, but unlike natural food rewards the lever pressing did not decline with satiation. When the number of presses required to receive a stimulation was altered, mice adjusted their rate of pressing accordingly, suggesting that the rate of stimulation was a controlled variable. Moreover, extinction, i.e. the cessation of action-contingent stimulation, and the complete reversal of the relationship between action and outcome by the imposition of an omission contingency, rapidly abolished lever pressing. Together these results suggest that selective activation of SNC DA neurons can be sufficient for acquisition and maintenance of a new instrumental action.

  18. Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults.

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    Yilmaz, R; Behnke, S; Liepelt-Scarfone, I; Roeben, B; Pausch, C; Runkel, A; Heinzel, S; Niebler, R; Suenkel, U; Eschweiler, G W; Maetzler, W; Berg, D

    2016-05-01

    Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre-motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B-mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established. Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo-constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN-). In both cohorts, SN+ individuals performed significantly worse than the SN- group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P Color-Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between-group effects were found in other cognitive tests and domains. These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN- independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD. © 2016 EAN.

  19. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain

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    Hyeok Gyu eKwon

    2014-02-01

    Full Text Available Objectives: Many animal and a few human studies have reported on the neural connectivity of the substantia nigra (SN and the ventral tegmental area (VTA. However, it has not been clearly elucidated so far. We attempted to investigate any differences in neural connectivity of the SN/VTA in the human brain, using diffusion tensor imaging (DTI.Methods: Sixty-three healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. Connectivity was defined as the incidence of connection between the SN/VTA and each brain regions in the brain.Results: The connectivity of SN was higher than that of the VTA. This included in the primary motor cortex, primary somatosensory cortex, premotor cortex, prefrontal cortex, caudate nucleus, globus pallidus, putamen, nucleus accumbens, temporal lobe, amygdala, pontine basis, occipital lobe, anterior and posterior lobe of cerebellum, corpus callosum, and external capsule (p.05.Conclusions: We found the differences in neural connectivity of the SN/VTA in the human brain. The method and results of this study can provide useful information for clinicians and researchers in neuroscience, especially who work for Parkinson’s disease and patients with brain injury.

  20. The somatodendritic domain of substantia nigra pars reticulata projection neurons in the rat.

    Science.gov (United States)

    Cebrián, Carolina; Parent, André; Prensa, Lucía

    2007-01-01

    We have examined the morphology of the somatodendritic domain of projection neurons located in different sectors of rat substantia nigra pars reticulata (SNr) or having distinct axonal arborizations. Forty-three neurons - 23 located in the dorsal half and 20 in the ventral half of SNr - were injected with biotinylated dextran amine and their somatodendritic domain was reconstructed from serial sagittal sections with a camera lucida. The axonal arborization of 14 neurons was also reconstructed. Dorsally located SNr neurons had a larger perikaryon, a higher number of primary dendrites and a more extensive dendritic arbor than the ventrally located ones. However, irrespective of their location in the SNr, the somatodendritic domain was always longer along the rostrocaudal axis than along the dorsoventral and mediolateral axes. Specific correlations between somatodendritic morphology and axonal arborization could be established for some SNr neurons, but among SNr neurons with similar efferent projections, those lying dorsally always exhibited a larger perikaryon and a more widespread dendritic arbor than those located ventrally. These results indicate that the morphology of the somatodendritic domain of SNr projection neurons is related to the location of their perikaryon within the structure rather than to the pattern of their axonal projections.

  1. Basal ganglia and thalamic input from neurons located within the ventral tier cell cluster region of the substantia nigra pars compacta in the rat.

    Science.gov (United States)

    Cebrián, Carolina; Prensa, Lucía

    2010-04-15

    The most caudally located dopaminergic (DA) ventral tier neurons of the substantia nigra pars compacta (SNc) form typical cell clusters that are deeply embedded in the substantia nigra pars reticulata (SNr). Here we examine the efferent projections of 35 neurons located in the SNr region where these SNc cell clusters reside. The neuronal cell body was injected with biotinylated dextran amine so as to trace each complete axon in the sagittal or the coronal plane. Electrophysiological guidance guaranteed that the tracer was ejected among neurons displaying a typical SNc discharge pattern. Furthermore, double immunofluorescence and immunohistochemical labeling ensured that the tracer deposits were placed within the DA cell clusters. Three types of projection neurons occurred in the SNc ventral tier cell cluster region: type I neurons, projecting to basal ganglia; type II neurons, targeting both the basal ganglia and thalamus; and type III neurons, projecting only to the thalamus. The striatum was targeted by most of the type I and II neurons and the innervation reached both the striosome/subcallosal streak and matrix compartments. Many nigrostriatal fibers provided collaterals to the globus pallidus and, less frequently, to the subthalamic nucleus. At a thalamic level, type II and III neurons preferentially targeted the reticular, ventral posterolateral, and ventral medial nuclei. Our results reveal that the SNr region where DA ventral tier cell clusters reside harbors neurons projecting to the basal ganglia and/or the thalamus, thus suggesting that neurodegeneration of nigral neurons in Parkinson's disease might affect various extrastriatal basal ganglia structures and multiple thalamic nuclei. (c) 2009 Wiley-Liss, Inc.

  2. The h-current in the substantia Nigra pars compacta neurons: a re-examination.

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    Cristina Gambardella

    Full Text Available The properties of the hyperpolarization-activated cation current (I(h were investigated in rat substantia nigra - pars compacta (SNc principal neurons using patch-clamp recordings in thin slices. A reliable identification of single dopaminergic neurons was made possible by the use of a transgenic line of mice expressing eGFP under the tyrosine hydroxylase promoter. The effects of temperature and different protocols on the I(h kinetics showed that, at 37°C and minimizing the disturbance of the intracellular milieu with perforated patch, this current actually activates at potentials more positive than what is generally indicated, with a half-activation potential of -77.05 mV and with a significant level of opening already at rest, thereby substantially contributing to the control of membrane potential, and ultimately playing a relevant function in the regulation of the cell excitability. The implications of the known influence of intracellular cAMP levels on I(h amplitude and kinetics were examined. The direct application of neurotransmitters (DA, 5-HT and noradrenaline physiologically released onto SNc neurons and known to act on metabotropic receptors coupled to the cAMP pathway modify the I(h amplitude. Here, we show that direct activation of dopaminergic and of 5-HT receptors results in I(h inhibition of SNc DA cells, whereas noradrenaline has the opposite effect. Together, these data suggest that the modulation of I(h by endogenously released neurotransmitters acting on metabotropic receptors -mainly but not exclusively linked to the cAMP pathway- could contribute significantly to the control of SNc neuron excitability.

  3. Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta

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    C.A. Santos

    2008-10-01

    Full Text Available Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc could be activated by gentle handling, a method to obtain sleep deprivation (SD. Adult male C57/BL6J mice (N = 5/group were distributed into non-SD (NSD or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg. After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2 exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold of neuronal activation may serve as a marker of SD.

  4. Dopaminergic Neurodegeneration in the Mouse Is Associated with Decrease of Viscoelasticity of Substantia Nigra Tissue.

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    Elisabeth G Hain

    Full Text Available The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD. Such alterations can be measured by magnetic resonance elastography (MRE as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1 the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN, midbrain and hippocampus in a mouse model of PD, and (2 if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and-to a lesser extent-elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation

  5. Dopaminergic Neurodegeneration in the Mouse Is Associated with Decrease of Viscoelasticity of Substantia Nigra Tissue.

    Science.gov (United States)

    Hain, Elisabeth G; Klein, Charlotte; Munder, Tonia; Braun, Juergen; Riek, Kerstin; Mueller, Susanne; Sack, Ingolf; Steiner, Barbara

    2016-01-01

    The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD). Such alterations can be measured by magnetic resonance elastography (MRE) as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1) the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN), midbrain and hippocampus in a mouse model of PD, and (2) if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP) treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and-to a lesser extent-elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation and diagnostics

  6. Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

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    Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

    2015-03-01

    Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

  7. Modulation of cardiac activity by tachykinins in the rat substantia nigra

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    Lessard, Andrée; Couture, Réjean

    2001-01-01

    The effects of tachykinin NK1, NK2 and NK3 receptor agonists and antagonists were measured on blood pressure (MAP) and heart rate (HR) after bilateral microinjection into the substantia nigra (SN) of awake, unrestrained rats. Increasing doses (25 pmol – 1 nmol) of selective agonists at NK1 ([Sar9,Met(O2)11]SP), NK2 ([β-Ala8]NKA(4 – 10)) and NK3 (senktide) receptors into the SN produced tachycardia which was selectively and reversibly blocked by the prior injection of tachykinin antagonists at NK1 (RP67580, 250 pmol), NK2 (SR48968, 250 pmol) and NK3 (R-820, 500 pmol) receptor. A rapid fall in MAP followed by a pressor response was seen with 1 nmol of [Sar9,Met(O2)11]SP. Behavioural activity was elicited by 1 nmol of [Sar9,Met(O211]SP (sniffing>face washing=grooming) and senktide (sniffing>wet dog shake>rearing=locomotion). Tachykinin antagonists had no direct cardiovascular or behavioural effects. The tachycardia produced by 100 pmol of [β-Ala8]NKA(4 – 10) or senktide was abolished by an i.v. treatment with atenolol (β1-adrenoceptor antagonist, 5 mg kg−1) while that evoked by [Sar9,Met(O2)11]SP was reduced. A combination of atenolol (5 mg kg−1) and atropine (muscarinic antagonist, 1 mg kg−1) blocked the response evoked by [Sar9,Met(O2)11]SP. These data suggest that the SN is a potential site of modulation of cardiac activity by tachykinins. In addition to the withdrawal of the cardiovagal activity by NK1 receptor, the three tachykinin receptors appear to increase the sympatho/adrenal drive to the heart. This occurs independently of changes in MAP and behaviour. Hence, this study highlights a new central regulatory mechanism of cardiac autonomic activity. PMID:11739252

  8. Sensory-motor processing in substantia nigra pars reticulata in conscious cats.

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    Schwarz, M; Sontag, K H; Wand, P

    1984-02-01

    Extracellular recordings were made with chronically implanted micro-electrodes from 109 substantia nigra neurones in conscious cats. Ninety-six of 109 neurones met the criteria of presumed non-dopaminergic pars reticulata (s.n.r.) neurones. Background discharge, in animals in a state of relaxed wakefulness and in the absence of overt movements, was in the range of 11-37 impulses/s, mean 19.2 impulses/s. The discharges of fifty-two of ninety-six neurones tested were modified by innocuous mechanical skin stimulation. Neurones responded chiefly to stimuli delivered to the contralateral body side. Responses generally comprised net excitation and occurred with short latency (range 10-34 ms; mean 17.3 ms). Convergence from both forelimbs or the contralateral fore- and hind limbs was evident in a few cases. One-fourth (twenty-four out of ninety-six) of the s.n.r. neurones tested were sensitive to passive manipulation of limb joints in the quiet, conscious cat and responded exclusively to angular displacement of one contralateral joint. Responses were directional and phasic. None of the s.n.r. neurones tested responded to clicks and/or light flashes. However, stimuli moving across the contralateral visual field substantially modified the discharge rate of ten out of ninety-six s.n.r. neurones. Responses were directional and invariably associated with eye movements. Animals were also trained to walk on a treadmill and to perform certain self-generated limb movements. S.n.r. neurones with a receptive field on a limb regularly showed modulations in discharge during locomotion, phase-related to the step cycle, and also short-latency responses during disturbance of such movements. Ten out of ninety-six s.n.r. neurones discharged almost exclusively prior to and during self-generated movements of a single limb. Their most powerful modulations in firing rate occurred, whenever an animal tried to overcome an external impediment or to resist an imposed movement. These observations

  9. Incremental conductance levels of GABAA receptors in dopaminergic neurones of the rat substantia nigra pars compacta.

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    Guyon, A; Laurent, S; Paupardin-Tritsch, D; Rossier, J; Eugène, D

    1999-05-01

    1. Molecular and biophysical properties of GABAA receptors of dopaminergic (DA) neurones of the pars compacta of the rat substantia nigra were studied in slices and after acute dissociation. 2. Single-cell reverse transcriptase-multiplex polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for the alpha3 subunit of the GABAA receptor, but further showed the presence of alpha4 subunit mRNAs. alpha2, beta1 and gamma1 subunit mRNAs were never detected. Overall, DA neurones present a pattern of expression of GABAA receptor subunit mRNAs containing mainly alpha3/4beta2/3gamma3. 3. Outside-out patches were excised from DA neurones and GABAA single-channel patch-clamp currents were recorded under low doses (1-5 microM) of GABA or isoguvacine, a selective GABAA agonist. Recordings presented several conductance levels which appeared to be integer multiples of an elementary conductance of 4-5 pS. This property was shared by GABAA receptors of cerebellar Purkinje neurones recorded in slices (however, with an elementary conductance of 3 pS). Only the 5-6 lowest levels were analysed. 4. A progressive change in the distribution of occupancy of these levels was observed when increasing the isoguvacine concentration (up to 10 microM) as well as when adding zolpidem (20-200 nM), a drug acting at the benzodiazepine binding site: both treatments enlarged the occupancy of the highest conductance levels, while decreasing that of the smallest ones. Conversely, Zn2+ (10 microM), a negative allosteric modulator of GABAA receptor channels, decreased the occupancy of the highest levels in favour of the lowest ones. 5. These properties of alpha3/4beta2/3gamma3-containing GABAA receptors would support the hypothesis of either single GABAA receptor channels with multiple open states or that of a synchronous recruitment of GABAA receptor channels that could involve their clustering in the membranes of DA neurones.

  10. Cognitive performance patterns in healthy individuals with substantia nigra hyperechogenicity and early Parkinson’s disease

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    Rezzak Yilmaz

    2016-11-01

    Full Text Available Introduction: Hyperechogenicity of the substantia nigra (SN+ is a risk marker for Parkinson’s disease (PD which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD.Methods: Data of 262 healthy individuals with normal echogenicity (SN- and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the Consortium to Establish a Registry for Alzheimer’s disease test battery. First, the test clusters (factors were identified using a principal component analysis (PCA. Mean group performance of cognitive tests belonging to distinct factors, according to the PCA, and single subtest performances were compared using analyses of variance. Second, the number of individuals with abnormal cognitive performances (z-score <-1.0 were compared between groups. Results: Verbal memory, semantic and executive function, and praxis were identified as components of cognitive performances. The SN+ group performed significantly worse than the SN- group in tests assessing semantic and executive function, with a non-significant decrease in verbal memory. On the subtest level, individuals of the SN+ group scored significantly lower than the SN- group on the Boston Naming Test (BNT (p=0.008. In all subtests, the percentages of PD patients with values below the cut-off for abnormal performance were higher than in the SN- group. Moreover, more individuals from the SN+ group scored below the cut-off in the BNT (SN-=8.4%, SN+=20.8%, p=0.01 and TMT-B (SN-=6.9%, SN+=16.7%, p=0.02, compared to the SN- group. Conclusion: This study confirms poorer performance of healthy individuals with SN+ compared to SN- in specific cognitive domains. However, against the SN- group, the cognitive

  11. Anti-apoptotic effect of Shudipingchan granule in the substantia nigra of rat models of Parkinson′s disease

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    Qing Ye

    2016-01-01

    Full Text Available Levodopa is the gold-standard treatment for Parkinson′s disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson′s disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily with or without Shudipingchan granule (7.5 mL/kg intragastrically, twice daily, for 4 weeks. The long-term use of levodopa accelerated apoptosis of nigral cells and worsened behavioral symptoms by activating the extracellular signal-regulated kinase pathway and downstream apoptotic factors. However, administration of Shudipingchan granule with levodopa reduced expression of phosphorylated extracellular signal-regulated kinase 1/2 and Bax, increased tyrosine hydroxylase and Bcl-2, reduced apoptosis in the substantia nigra, and markedly improved dyskinesia. These findings suggest that Shudipingchan granule suppresses neuronal apoptosis by inhibiting the hyperphosphorylation of extracellular signal-regulated kinase and downregulating expression of anti-apoptotic genes. Shudipingchan granule, used in combination with levodopa, can effectively reduce the symptoms of Parkinson′s disease.

  12. Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

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    Smeyne, Richard Jay; Breckenridge, Charles B.; Beck, Melissa; Jiao, Yun; Butt, Mark T.; Wolf, Jeffrey C.; Zadory, Dan; Minnema, Daniel J.; Sturgess, Nicholas C.; Travis, Kim Z.; Cook, Andrew R.; Smith, Lewis L.; Botham, Philip A.

    2016-01-01

    The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased

  13. Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson's disease

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    Groeger, Adriane; Godau, Jana; Berg, Daniela [University of Tuebingen, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Disease (DZNE), Tuebingen (Germany); Chadzynski, Grzegorz; Klose, Uwe [University Hospital Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Tuebingen (Germany)

    2011-09-15

    To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252 ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls. (orig.)

  14. Does the cerebral cortex exacerbate dopaminergic cell death in the substantia nigra of 6OHDA-lesioned rats?

    Science.gov (United States)

    Luquin, Natasha; Mitrofanis, John

    2008-01-01

    We have explored the survival of dopaminergic cells of the substantia nigra pars compacta (SNc) in 6 hydroxydopamine (6OHDA)-lesioned rats with prior cortical removal. There were approximately 35% more dopaminergic cells in the ventral sector of SNc (vSNc) of 6OHDA-lesioned rats that had prior cortical removal compared to those that did not. By contrast, there were no differences in dopaminergic cell number between these experimental groups in the ventral tegmental area (VTA) and the dorsal sector of SNc (dSNc). Hence, prior cortical removal in 6OHDA-lesioned rats neuroprotected vSNc--but not VTA or dSNc--dopaminergic cells from death.

  15. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    Science.gov (United States)

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Neuromelanin imaging of the substantia nigra and locus ceruleus among patients with Parkinson's disease using 3Tesla MRI

    International Nuclear Information System (INIS)

    Konno, Kanako; Ohtsuka, Chigumi; Kato, Kanako; Terayama, Yasuo

    2010-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder in which loss of dopaminergic neurons from the pars compacta of substantia nigra (SNc) and locus ceruleus (LC) in the major pathologic substrate. To investigate the relationships between the loss of SNc and LC neurons, and the stage of illness, we compared the signal intensity of SNc and LC between PD patients and normal controls by using a neuromelanin-sensitive magnetic resonance imaging (MRI) at 3 Tesla. We examined 41 PD patients in early stage, 10 in progressive stage, and 22 healthy controls. In PD, we observed a significant loss of neuromelanin in LC (p<0.0001) and lateral area of SNc (p=0.0011) while no significant difference between neuromelanin imaging and severity of PD was observed. The present study suggests that neuromelanin imaging using 3T MRI is a useful tool for early diagnosis of Parkinson's disease. (author)

  17. Excitatory drive from the Subthalamic nucleus attenuates GABAergic transmission in the Substantia Nigra pars compacta via endocannabinoids.

    Science.gov (United States)

    Freestone, Peter S; Wu, Xi Hau; de Guzman, Gabriel; Lipski, Janusz

    2015-11-15

    Endocannabinoids (eCBs) are cannabis-like substances produced in the brain where their primary function is to regulate synaptic transmission by inhibiting neurotransmitter release in a retrograde fashion. We have recently demonstrated a novel mechanism regulating GABAergic transmission from neurons in the Substantia Nigra pars reticulata (SNr) to dopaminergic neurons in the Substantia Nigra pars compacta (SNc) mediated by eCBs. Production of eCBs was initiated by spillover of glutamate, yet the source of the glutamate was not determined (Freestone et al., 2014; Neuropharmacology 79 p467). The present study aimed at elucidating the potential role of glutamatergic terminals arising from neurons in the Subthalamic nucleus (STN) in driving the eCB-mediated modulation of this inhibitory transmission. GABAergic IPSCs or IPSPs evoked in SNc neurons by electrical stimuli delivered to the SNr region were transiently inhibited by electrical or pharmacological (U-tube application of muscarinic agonist carbachol [100 µM]) stimulation of the STN (to 74±5% and 69±4% respectively). In both stimulation protocols, the attenuation of GABAergic transmission was abolished by cannabinoid receptor 1 antagonist rimonabant (3 µM), and reduced by group 1 metabotropic glutamate receptor antagonist CPCCOEt (100 µM), consistent with a glutamate-initiated and eCB-mediated mechanism. The carbachol-induced attenuation of GABAergic transmission was abolished by M3 muscarinic receptor antagonist 4-DAMP (10 µM), confirming a specific activation of STN neurons. These results demonstrate that glutamatergic projection from the STN to dopaminergic SNc neurons underlies an eCB-mediated inhibition of GABAergic input to these neurons. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients

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    Iadarola, M.J.; Ofri, D.; Kleinman, J.E. (National Institute of Dental Research, Bethesda, MD (USA) National Institute of Mental Health, Washington, DC (USA))

    1991-01-01

    Three peptide neuromodulators that are found in high concentration in the subtantia nigra: dynorphin A 1,8-met5-enkephalin-arg6-gly7-leu8 and substance P, were measured by specific radioimmunoassays in nigral tissue from normals and schizophrenics postmortem. Substance P and dynorphin were unchanged between the two groups. However, the proenkephalin-derived peptide was significantly elevated in the schizophrenic group. The immunoreactivity was identified as authentic met5-enkephalin-arg6-gly7-leu8 by high pressure liquid chromatography. The data suggest that a different set of regulatory controls exists for nigral enkephalin peptides as compared to dynorphin and substance P, and that the former system may be disordered in schizophrenia.

  19. Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat.

    Science.gov (United States)

    Cebrián, Carolina; Parent, André; Prensa, Lucía

    2005-11-21

    Axons from neurons of the rat substantia nigra pars reticulata (SNr) and pars lateralis (SNl) were traced after injecting their cell body with biotinylated dextran amine. Thirty-two single axons were reconstructed from serial sagittal sections with a camera lucida, whereas four other SNr axons were reconstructed in the coronal plane to determine whether they innervate the contralateral hemisphere. Four distinct types of SNr projection neurons were identified based on their main axonal targets: type I neurons that project to the thalamus; type II neurons that target the thalamus, the superior colliculus (SC), and the pedunculopontine tegmental nucleus (PPTg); type III neurons that project to the periaqueductal gray matter and the thalamus; and type IV neurons that target the deep mesencephalic nucleus (DpMe) and the SC. The axons of the SNl showed the same branching patterns as SNr axons of types I, II, and IV. The coronal reconstructions demonstrated that SNr neurons innervate the thalamus, the SC, and the DpMe bilaterally. At the thalamic level, SNr and SNl axons targeted preferentially the ventral medial, ventral lateral, paracentral, parafascicular, and mediodorsal nuclei. Axons reaching the SC arborized selectively within the deep layers of this structure. Our results reveal that the SNr and SNl harbor several subtypes of projection neurons endowed with a highly patterned set of axon collaterals. This organization allows single neurons of these output structures of the basal ganglia to exert a multifaceted influence on a wide variety of diencephalic and midbrain structures. (c) 2005 Wiley-Liss, Inc.

  20. Neuropeptide S Increases locomotion activity through corticotropin-releasing factor receptor 1 in substantia nigra of mice.

    Science.gov (United States)

    Li, M S; Peng, Y L; Jiang, J H; Xue, H X; Wang, P; Zhang, P J; Han, R W; Chang, M; Wang, R

    2015-09-01

    Neuropeptide S (NPS), the endogenous ligand of NPS receptor (NPSR), was reported to be involved in the regulation of arousal, anxiety, locomotion, learning and memory. The basal ganglia play a crucial role in regulating of locomotion-related behavior. Here, we found that NPSR protein of mouse was distributed in the substantia nigra (SN) and globus pallidus (LGP) by immunohistochemical analysis. However, less is known about the direct locomotion-related effects of NPS in both SN and LGP. Therefore, we investigated the role of NPS in locomotion processes, using the open field test. The results showed that NPS infused into the SN (0.03, 0.1, 1nmol) or LGP (0.01, 0.03, 0.1nmol) dose-dependently increased the locomotor activity in mice. SHA 68 (50mg/kg), an antagonist of NPSR, blocked the locomotor stimulant effect of NPS in both nuleus. Meanwhile, these effects of NPS were also counteracted by the CRF1 receptor antagonist antalarmin (30mg/kg, i.p.). In addition, we found that the expression of c-Fos was significantly increased after NPS was delivered into SN. In conclusion, these results indicate that NPS-NPSR system may regulate locomotion together with the CRF1 system in SN. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Motor stimulant effects of ethanol injected into the substantia nigra pars reticulata: importance of catalase-mediated metabolism and the role of acetaldehyde.

    Science.gov (United States)

    Arizzi-LaFrance, Maria N; Correa, Mercè; Aragon, Carlos M G; Salamone, John D

    2006-05-01

    A series of experiments was conducted to investigate the locomotor effects of local injections of ethanol and the ethanol metabolite, acetaldehyde, into substantia nigra pars reticulata (SNr). Infusions of ethanol into SNr resulted in a dose-related increase in locomotor activity, with maximal effects at a dose of 1.4 micromol. Ethanol injected into a control site dorsal to substantia nigra failed to stimulate locomotion, and another inactive site was identified in brainstem areas posterior to substantia nigra. The locomotor effects of intranigral ethanol (1.4 micromol) were reduced by coadministration of 10 mg/kg sodium azide, a catalase inhibitor that acts to reduce the metabolism of ethanol into acetaldehyde in the brain. SNr infusions of acetaldehyde, which is the first metabolite of ethanol, also increased locomotion. Taken together, these results indicate that SNr is one of the sites at which ethanol and acetaldehyde may be acting to induce locomotor activity. These results are consistent with the hypothesis that acetaldehyde is a centrally active metabolite of ethanol, and provide further support for the idea that catalase activity is a critical step in the regulation of ethanol-induced motor activity. These studies have implications for understanding the brain mechanisms involved in mediating the ascending limb of the biphasic dose-response curve for the effect of ethanol on locomotor activity.

  2. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra

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    Purves-Tyson Tertia D

    2012-08-01

    Full Text Available Abstract Background Increased risk of schizophrenia in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission are found and most studies address this in adult animals. Testosterone-dependent actions in neurons are direct via activation of androgen receptors (AR or indirect by conversion to 17β-estradiol and activation of estrogen receptors (ER. How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s and the level of steroid conversion enzymes (aromatase and 5α-reductase. We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT and monoamine oxygenase (MAO A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of aromatase and 5α-reductase mRNA levels. Results We find ERα and AR in midbrain dopamine neurons in adolescent male rats, indicating that dopamine neurons are poised to respond to circulating sex steroids. We report that androgens (T and DHT increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra. We report that all three sex steroids increase AR mRNA. Differential action on ER pathways, with ERα mRNA down-regulation and ERβ mRNA up-regulation by testosterone was found. 5α reductase-1 mRNA was increased by AR activation, and aromatase mRNA was decreased by gonadectomy. Conclusions We conclude that increased testosterone at adolescence can shift the balance of sex steroid signaling to favor androgenic responses through promoting

  3. Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits.

    Science.gov (United States)

    Liu, Yuxin; Qin, Liya; Wilson, Belinda; Wu, Xuefei; Qian, Li; Granholm, Ann-Charlotte; Crews, Fulton T; Hong, Jau-Shyong

    2008-09-01

    We have previously reported that a single injection of endotoxin, lipopolysaccharide (LPS, 5mg/kg, i.p.), causes a delayed and progressive loss of TH-IR neurons in the substantia nigra (SN) in C57BL/six male mice. In this study, we determined sex differences and behavioral deficits accompanying the loss of TH-IR neurons in response to peripheral LPS injection. A single injection of LPS (5mg/kg, i.p.) failed to produce any loss of TH-IR neurons in the SN of female mice over a 12-month period. To determine if multiple-injections were required, female mice received five injections of LPS (5mg/kg, i.p.) at either weekly or monthly intervals. Behavioral motor ability and TH-IR neuronal loss were determined after the first injection of LPS. We found significant differences in both behavioral activities and neuronal loss between these two injection paradigms. Between 7 and 20 months after the first injection of LPS, progressive behavioral changes, measured by rotor-rod and open-field activities, and neuronal loss in SN were observed in monthly injected, but not in weekly injected mice. In addition, reduced rotor-rod ability in monthly injected mice were restored following treatment of l-dopa/carbidopa (30 mg/3mg/kg), i.p.). Approximately 40 and 50% loss of TH-IR neurons at 9 and 20 months, respectively, was observed after exposure to LPS, suggesting that the behavioral deficit is related to loss of dopamine function in the nigra-striatal pathway. More intense immuno-staining of alpha-synuclein and inflammatory markers were detected in brain sections exposed to LPS. In conclusion, these results show that multi-LPS monthly injections can induce a delayed and progressive loss of TH-IR neurons and motor deficits which resemble the progressive nature of Parkinson's disease. Further, the present study reveals a clear sex difference: female mice are more resistant to LPS than male mice. Repeated monthly LPS injections are required to cause both motor behavioral deficits and DA

  4. Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

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    Diego Iacono

    2015-05-01

    Full Text Available Background: Dystonias (Dys represent the third most common movement disorder after essential tremor (ET and Parkinson's disease (PD. While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG, and specifically in the substantia nigra (SN. Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age‐matched control subjects (C. Results: We observed a significant reduction (∼20% of pigmented neurons in the SN of Dys compared to C (p<0.01. Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co‐occurring SN pathologies including Lewy pathology, tau‐neurofibrillary tangles, β‐amyloid deposits, ubiquitin (ubiq, and phosphorylated‐TAR DNA‐binding protein 43 (pTDP43‐positive inclusions. Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

  5. Iptakalim inhibits nicotinic acetylcholine receptor-mediated currents in dopamine neurons acutely dissociated from rat substantia nigra pars compacta.

    Science.gov (United States)

    Hu, J; DeChon, J; Yan, K C; Liu, Q; Hu, G; Wu, J

    2006-07-31

    Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human alpha4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 microM), while whole-cell currents induced by ACh (1 mM+1 microM atropine) or an alpha4beta2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 microM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, alpha4-containing nAChRs, rather than ionotropic glutamate receptors, GABA(A) receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles.

  6. Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron activity in the substantia nigra of patients with schizophrenia.

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    Yoshiyuki Watanabe

    Full Text Available PURPOSE: The dopamine hypothesis suggests that excessive dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI in patients with schizophrenia and healthy control subjects. METHODS: We prospectively examined 52 patients with schizophrenia (M: F = 27∶25, mean age, 35 years and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc, midbrain tegmentum, locus ceruleus (LC, and pons. We then calculated the contrast ratios (CR for the SNc (CRSN and LC (CRLC, which were compared between patients and healthy controls using unpaired t-tests. RESULTS: The SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.89±2.37 vs. 9.6±2.36, p<0.01. We observed no difference in the CRLC values between the patients and healthy controls (14.21±3.5 vs. 13.44±3.37, p = 0.25. Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls. CONCLUSIONS: Neuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Our results indicate the presence of excessive dopamine products in the SNc of these patients.

  7. Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

    Science.gov (United States)

    Pyatigorskaya, Nadya; Gaurav, Rahul; Arnaldi, Dario; Leu-Semenescu, Smaranda; Yahia-Cherif, Lydia; Valabregue, Romain; Vidailhet, Marie; Arnulf, Isabelle; Lehéricy, Stephane

    2017-11-01

    Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2*, and diffusion tensor measures were quantified in the SN. Additionally, two raters performed visual analysis of the SN using the NM-sensitive images. Participants with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls, but showed no differences in axial, radial, or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the receiver operating characteristic analysis discriminated between participants with iRBD and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The three biomarkers had a combined accuracy of 0.92. The fraction of participants correctly characterized by visual assessment was 0.81. NM-sensitive imaging and FA allowed for the detection of SN damage in participants with iRBD with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  8. Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

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    Wuisman Piet GWM

    2007-09-01

    Full Text Available Abstract Background Parkinson's disease (PD is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin. Methods/Design We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain. Discussion As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process. Trial registration (ITRSCC NCT00368199

  9. Vitamin B12-impaired metabolism produces apoptosis and Parkinson phenotype in rats expressing the transcobalamin-oleosin chimera in substantia nigra.

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    Carlos Enrique Orozco-Barrios

    Full Text Available BACKGROUND: Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII to the reticulum through its fusion with Oleosin (OLEO. METHODOLOGY: Gene constructs including transcobalamin-oleosin (TCII-OLEO and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO, oleosin-transcobalamin (OLEO-TCII, TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids. PRINCIPAL FINDINGS: The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids. CONCLUSIONS/SIGNIFICANCE: In conclusion, the TCII-OLEO transfection

  10. The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy.

    Science.gov (United States)

    Akman, Ozlem; Gulcebi, Medine I; Carcak, Nihan; Ketenci Ozatman, Sema; Eryigit, Tugba; Moshé, Solomon L; Galanopoulou, Aristea S; Onat, Filiz Yilmaz

    2015-11-01

    Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior . In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in

  11. Nuclear microscopic investigations into the elemental changes in the substantia nigra of unilaterally MPTP-lesioned Parkinsonian monkeys

    Science.gov (United States)

    Thong, P. S. P.; He, Y.; Lee, T.; Watt, F.

    1997-07-01

    Various transition metals, particularly iron, have been implicated in the aetiology of the neurodegenerative disease, Parkinson's disease, in which there is a characteristic loss of cells in the substantia nigra (SN) region of the brain. In this study, monkeys were unilaterally lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to obtain primate models of parkinsonism, with the non-lesioned side of the brain serving as controls. The monkeys were sacrificed at one day, one week, two weeks, one month and one year after lesioning to investigate the time dependent elemental changes in the parkinsonian SN. Sections of the brain encompassing both the lesioned and non-lesioned SNs were analysed using the National University of Singapore nuclear microscope. Adjacent sections were tyrosine hydroxylase (TH) immunohistochemically stained to provide complementary information on dopaminergic cell loss and to facilitate definition of the SN boundaries during data analysis. In one-day and one-week monkeys (representing early stages of the disease), there were no changes in elemental concentrations within experimental errors and the adjacent TH-stained sections did not show apparent cell loss in the SN. At two weeks, cell loss was seen in the lesioned SN compared to the control SN. Although there was no bulk increase in SN iron, localised accumulation of iron in granules containing up to 15% by weight iron was observed in the lesioned SN of one of the two-week monkeys. An average 15% increase in nigral iron, significant at the 90% confidence level ( p cell loss in the lesioned SN. In one-year samples (representing the advanced stage of the disease) there was a significant ( p cells in the lesioned SN was apparent from the adjacent TH-stained sections. These preliminary results suggest that while bulk increase in iron may seem to follow cell death, localised accumulation of SN iron in the early stages of the disease may play an important role in

  12. Seed point discontinuity-based segmentation method for the substantia nigra and the red nucleus in quantitative susceptibility maps.

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    Guo, Tian; Song, Yang; Li, Jianqi; Fan, Mingxia; Yan, Xu; He, Andi; Huang, Dongya; Shen, Chaomin; Zhang, Guixu; Yang, Guang

    2018-03-31

    The automatic segmentation of cerebral nuclei in the quantitative susceptibility mapping (QSM) images can provide assistance for surgical treatment and pathological mechanism studies. However, as the most frequently used segmentation method, the atlas method provides unsatisfactory results when segmenting the substantia nigra (SN) and the red nucleus (RN). To propose and evaluate an improved automatic method based on seed points-discontinuity for segmentations of the SN and the RN in QSM images. Prospective. In all, 22 subjects, 11 patients with Parkinson's disease (PD), and 11 healthy subjects (mean age of 68.0 ± 6.9 years) underwent MR scans. 3T system and a 3D multiecho gradient echo sequence with monopolar readout gradient. Manual segmentations by two radiologists (both with over 10 years of experience in neuroimaging) were used to establish a baseline for assessment. The Dice coefficient and the center-of-gravity distance was employed to evaluate the segmentation accuracy. The mean value and standard deviation of the Dice coefficient and center-of-gravity distance were calculated separately to compare segmentation results from the proposed method, the level set method, the atlas method (including the single-atlas method and the multi-atlas majority voting method). The statistical results of Dice coefficient of the SN and the RN between the ground truth and the segmentation were 0.79 ± 0.14 and 0.77 ± 0.06 for the proposed method, 0.40 ± 0.10 and 0.65 ± 0.09 for the level set method, 0.68 ± 0.09 and 0.64 ± 0.07 for the single-atlas method, 0.70 ± 0.06 and 0.68 ± 0.05 for the multi-atlas majority voting method, respectively. The proposed method also provides the lowest center-of-gravity distance value (1.05 ± 0.71 for the SN and 0.74 ± 0.35 for the RN). The segmentation results of the proposed method performed well on the in vivo data and were closer to the manual segmentation than the atlas method. 1

  13. Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models.

    Science.gov (United States)

    Sun, Xiao-Long; Chen, Bei-Yu; Zhao, Hai-Kang; Cheng, Ying-Ying; Zheng, Min-Hua; Duan, Li; Jiang, Wen; Chen, Liang-Wei

    2016-07-08

    Reactive astrogliosis is a remarkable pathogenetic hallmark of the brains of Parkinson's disease (PD) patients, but its progressive fate and regulation mechanisms are poorly understood. In this study, growth arrest specific 1 (Gas1), a tumor growth suppressor oncogene, was identified as a novel modulator of the cell apoptosis of reactive astrocytes in primary culture and the injured substantia nigra. Animal models and cell cultures were utilized in the present study. Lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated animal models were used to detect Gas1 expression in the brain via immunohistochemistry and western blot. Cell cultures were performed to analyze Gas1 functions in the viability and apoptosis of reactive astrocytes and SH-SY5Y cells by double labeling, CCK-8, LDH, TUNEL, flow cytometry, and siRNA knockdown methods. Gas1 expressions were significantly elevated in the majority of the reactive astrocytes of the brains with LPS or MPTP insults. In the injured substantia nigras, GFAP-positive astrocytes exhibited higher levels of cleaved caspase-3. In cell culture, the up-regulated Gas1 expression induced apoptosis of reactive astrocytes that were insulted by LPS in combination with interferon-γ and tumor necrosis factor-a. This effect was confirmed through siRNA knockdown of Gas1 gene expression. Finally and interestingly, the potential underlying signaling pathways were evidently related to an increase in the Bax/Bcl-2 ratio, the abundant generation of reactive oxygen species and the activation of cleaved caspase-3. This study demonstrated that the up-regulation of inducible Gas1 contributed to the apoptosis of reactive astrocytes in the injured nigra. Gas1 signaling may function as a novel regulator of astrogliosis and is thus a potential intervention target for inflammatory events in PD conditions.

  14. Recovery of dopamine neuronal transporter but lack of change of its mRNA in substantia nigra after inactivation by a new irreversible inhibitor characterized in vitro and ex vivo in the rat

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    Do Régo, Jean-Claude; Syringas, Maria; Leblond, Bertrand; Costentin, Jean; Bonnet, Jean-Jacques

    1999-01-01

    In vitro, the ability of DEEP-NCS {1-[2-(diphenylmethoxy)ethyl]-4-[2-(4-isothiocyanatophenyl)ethyl]-piperazine} to inhibit [3H]-dopamine uptake by rat striatal synaptosomes was concentration-dependent and inversely related to the protein concentration. This inhibition was irreversible and resulted from changes in Vmax and KM. DEEP-NCS was less potent on noradrenaline, serotonin and choline transport. One day after intrastriatal injections of DEEP-NCS (100 and 1000 pmol) in 20% dimethylsulphoxide, moderate decreases in the ex vivo dopamine uptake were observed in synaptosomes obtained from striatum injected with DEEP-NCS or solvent, and the contralateral uninjected striatum. In similar conditions, 300 pmol DEEP-NCS in 45% 2 hydroxypropyl-γ-cyclodextrin–0.5% dimethylsulphoxide solution sub-totally reduced ex vivo dopamine uptake and mazindol binding, and moderately decreased choline and serotonin transport. These reductions were specific to DEEP-NCS-injected striata. A clomipramine pretreatment (16 mg kg−1 i.p. 1 h before) was performed in following experiments, since it reduced the DEEP-NCS-elicited decrease in serotonin uptake without affecting other indices. One day after intrastriatal injection, DEEP-NCS elicited similar dose-dependent decreases in ex vivo dopamine uptake and mazindol binding (ID50=6.9-8 ng striatum−1). Changes in KM and Vmax for ex vivo dopamine transport produced by DEEP-NCS disappeared according to similar time-courses. The t½ for transporter recovery was 6.1 days. This value should correspond to its actual turnover rate in vivo, since no change in transporter mRNA level was observed in substantia nigra ipsilateral to 300 pmol DEEP-NCS-injected striatum. The results indicate that DEEP-NCS behaves as a potent, quite selective, irreversible inhibitor of the DAT, in vitro and in vivo. Its use in vivo suggests that the physiological half-life of the rat striatal DAT is close to 6 days. PMID:10498834

  15. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

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    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  16. Secondary parkinsonism due to focal substantia nigra lesions. A PET study with [18F]FDG and [18F]fluorodopa

    International Nuclear Information System (INIS)

    Boecker, H.; Weindl, A.; Kruggel, F.; Graerin v. Einsiedel, H.; Contrad, B.; Leenders, K.; Antonini, A.; Kuwert, T.

    1996-01-01

    We present a 71 year old woman with predominantly right sided parkinsonim of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [ 18 F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [ 18 F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions. (au) 39 refs

  17. Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra.

    Science.gov (United States)

    Heng, Yang; Zhang, Qiu-Shuang; Mu, Zheng; Hu, Jin-Feng; Yuan, Yu-He; Chen, Nai-Hong

    2016-01-22

    Parkinson's disease (PD) is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of aggregated α-synuclein in specific central nervous system (CNS) regions. Disease development is attributed to α-synuclein abnormalities, particularly aggregation and phosphorylation. The ginsenoside Rg1, an active component of ginseng, possesses neuroprotective and anti-inflammatory effects. The purpose of the present study was to evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNpc. Rg1 also alleviated the unusual MPTP-induced increase in oligomeric, phosphorylated and disease-related α-synuclein in the SNpc. In conclusion, Rg1 protects dopaminergic neurons, most likely by reducing aberrant α-synuclein-mediated neuroinflammation, and holds promise for PD therapeutics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Protein aggregation containing beta-amyloid, alpha-synuclein and hyperphosphorylated tau in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure

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    Martins Stephanie A

    2010-11-01

    Full Text Available Abstract Background Protein aggregates containing alpha-synuclein, beta-amyloid and hyperphosphorylated tau are commonly found during neurodegenerative processes which is often accompanied by the impairment of mitochondrial complex I respiratory chain and dysfunction of cellular systems of protein degradation. In view of this, we aimed to develop an in vitro model to study protein aggregation associated to neurodegenerative diseases using cultured cells from hippocampus, locus coeruleus and substantia nigra of newborn Lewis rats exposed to 0.5, 1, 10 and 25 nM of rotenone, which is an agricultural pesticide, for 48 hours. Results We demonstrated that the proportion of cells in culture is approximately the same as found in the brain nuclei they were extracted from. Rotenone at 0.5 nM was able to induce alpha-synuclein and beta amyloid aggregation, as well as increased hyperphosphorylation of tau, although high concentrations of this pesticide (over 1 nM lead cells to death before protein aggregation. We also demonstrated that the 14kDa isoform of alpha-synuclein is not present in newborn Lewis rats. Conclusion Rotenone exposure may lead to constitutive protein aggregation in vitro, which may be of relevance to study the mechanisms involved in idiopathic neurodegeneration.

  19. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  20. In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity.

    Science.gov (United States)

    Shamoto-Nagai, M; Maruyama, W; Hashizume, Y; Yoshida, M; Osawa, T; Riederer, P; Naoi, M

    2007-01-01

    alpha-Synuclein (alphaSYN) plays a central role in the neural degeneration of Parkinson's disease (PD) through its conformational change. In PD, alphaSYN, released from the membrane, accumulates in the cytoplasm and forms Lewy body. However, the mechanism behind the translocation and conformational change of alphaSYN leading to the cell death has not been well elucidated. This paper reports that in the dopamine neurons of the substantia nigra containing neuromelanin from PD patients, alphaSYN was modified with acrolein (ACR), an aldehyde product of lipid peroxidation. Histopathological observation confirmed the co-localization of protein immunoreactive to anti-alphaSYN and ACR antibody. By Western blot analyses of samples precipitated with either anti-alphaSYN or anti-ACR antibody, increase in ACR-modified alphaSYN was confirmed in PD brain. Modification of recombinant alphaSYN by ACR enhanced its oligomerization, and at higher ACR concentrations alphaSYN was fragmented and polymerized forming a smear pattern in SDS-PAGE. ACR reduced 20S proteasome activity through the direct modification of the proteasome proteins and the production of polymerized ACR-modified proteins, which inhibited proteasome activity in vitro. These results suggest that ACR may initiate vicious cycle of modification and aggregation of proteins, including alphaSYN, and impaired proteolysis system, to cause neuronal death in PD.

  1. Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

    Science.gov (United States)

    Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

    2018-01-17

    Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

  2. Neuroprotective changes in degeneration-related gene expression in the substantia nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray analysis

    Directory of Open Access Journals (Sweden)

    Sujung Yeo

    2015-03-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931 probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication.

  3. A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging.

    Science.gov (United States)

    Moon, Won-Jin; Park, Ju-Yeon; Yun, Won-Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Heejin; Kwak, Ki-Chang; Lee, Jong-Min; Han, Seol-Heui

    2016-01-01

    Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.

  4. Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis

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    Hirata, Fabiana C.C.; Vieira, Gilson; Lucato, Leandro T.; Leite, Claudia C.; Pastorello, Bruno F.; Otaduy, Maria C.G.; Chaim, Khallil T.; Campanholo, Kenia R. [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Sato, Joao R. [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Universidade Federal do ABC, Center of Mathematics, Computation and Cognition, Santo Andre (Brazil); Bor-Seng-Shu, Edson; Novaes, Natalia P. [Hospital Israelita Albert Einstein, Sao Paulo (Brazil); University of Sao Paulo, Department of Neurology, Sao Paulo (Brazil); Magalhaes Melo, Luciano; Goncalves, Marcia R.; Reis Barbosa, Egberto [University of Sao Paulo, Department of Neurology, Sao Paulo (Brazil); Pereira do Nascimento, Felipe Barjud; Amaro, Edson [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Jacobsen Teixeira, Manoel [University of Sao Paulo, Department of Neurosurgery, Sao Paulo (Brazil); Cardoso, Ellison Fernando [University of Sao Paulo, LIM-44, Department of Radiology, Sao Paulo, SP (Brazil); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Institute of Mathematics and Statistics University of Sao Paulo (IME-USP), Sao Paulo (Brazil)

    2017-06-15

    Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I{sup 2} = 91.9 %). SN-FA cannot be used as an isolated measure to diagnose PD. (orig.)

  5. Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches

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    Trujillo, Paula [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States); Summers, Paul E.; Costa, Antonella [Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI (Italy); Smith, Alex K. [University of Oxford, Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, Oxford (United Kingdom); Smith, Seth A. [Vanderbilt University Institute of Imaging Science, Nashville, TN (United States); Vanderbilt University, Department of Biomedical Engineering, Nashville, TN (United States); Mainardi, Luca T.; Cerutti, Sergio [Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, MI (Italy); Claassen, Daniel O. [Vanderbilt University Medical Center, Department of Neurology, Nashville, TN (United States)

    2017-12-15

    We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times (T{sub 2}{sup f}, T{sub 2}{sup m}) and rate of MT exchange between pools (k{sub mf}) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods. PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50). The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible. (orig.)

  6. Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra in a dopamine-dependent manner

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    Klaissle Philipp

    2012-10-01

    Full Text Available Abstract Background Parkinson’s disease is characterized by a continuous loss of neurons within the substantia nigra (SN leading to a depletion of dopamine. Within the adult SN as a non-neurogenic region, cells with mainly oligodendrocytic precursor characteristics, expressing the neuro-glial antigen-2 (NG2 are continuously generated. Proliferation of these cells is altered in animal models of Parkinson’s disease (PD. Exercise and environmental enrichment re-increase proliferation of NG2+ cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2+ cells can differentiate into oligodendrocytes but also into microglia and neurons as observed in vitro suggesting a possible hint for endogenous regenerative capacity of the SN. We investigated the role of dopamine in NG2-generation and differentiation in the adult SN stimulated by physical activity and environmental enrichment. Results We used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-model for dopamine depletion and analysed newborn cells in the SN at different maturation stages and time points depending on voluntary physical activity, enriched environment and levodopa-treatment. We describe an activity- induced increase of new NG2-positive cells and also mature oligodendrocytes in the SN of healthy mice. Running and enriched environment refused to stimulate NG2-generation and oligodendrogenesis in MPTP-mice, an effect which could be reversed by pharmacological levodopa-induced rescue. Conclusion We suggest dopamine being a key regulator for activity-induced generation of NG2-cells and oliogodendrocytes in the SN as a potentially relevant mechanism in endogenous nigral cellular plasticity.

  7. 3D neuromelanin-sensitive magnetic resonance imaging with semi-automated volume measurement of the substantia nigra pars compacta for diagnosis of Parkinson's disease

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    Ogisu, Kimihiro; Shirato, Hiroki [Hokkaido University Graduate School of Medicine, Department of Radiology, Hokkaido (Japan); Kudo, Kohsuke; Sasaki, Makoto [Iwate Medical University, Division of Ultrahigh Field MRI, Iwate (Japan); Sakushima, Ken; Yabe, Ichiro; Sasaki, Hidenao [Hokkaido University Hospital, Department of Neurology, Hokkaido (Japan); Terae, Satoshi; Nakanishi, Mitsuhiro [Hokkaido University Hospital, Department of Radiology, Hokkaido (Japan)

    2013-06-15

    Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD. We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle. Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC). The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (>2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86. Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD. (orig.)

  8. Differential neuroprotective and anti-inflammatory effects of L-type voltage dependent calcium channel and ryanodine receptor antagonists in the substantia nigra and locus coeruleus.

    Science.gov (United States)

    Hopp, Sarah C; Royer, Sarah E; D'Angelo, Heather M; Kaercher, Roxanne M; Fisher, David A; Wenk, Gary L

    2015-03-01

    Neuroinflammation and degeneration of catecholaminergic brainstem nuclei occur early in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Neuroinflammation increases levels of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal calcium (Ca(+2)) homoeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Alterations in Ca(+2) channel activity in the SN and LC can lead to disruption of normal pacemaking activity in these areas, contributing to behavioral deficits. Here, we utilized an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose (0.25 μg/h) of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28 days. Rats were treated with either the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. LPS-infused rats had significant motor deficits in the accelerating rotarod task as well as abnormal behavioral agitation in the forced swim task and open field. Corresponding with these behavioral deficits, LPS-infused rats also had significant increases in microglia activation and loss of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra pars compacta (SNpc) and locus coeruleus (LC). Treatment with nimodipine or dantrolene normalized LPS-induced abnormalities in the rotarod and forced swim, restored the number of TH-immunoreactive cells in the LC, and significantly reduced microglia activation in the SNpc. Only nimodipine significantly reduced microglia activation in the LC, and neither drug increased TH immunoreactivity in the SNpc. These findings demonstrate that the Ca(+2) dysregulation in the LC and SN brainstem nuclei is differentially altered by chronic neuroinflammation. Overall, targeting Ca + 2 dysregulation may be an important target for ameliorating neurodegeneration in the SNpc and LC.

  9. Regulation of substantia nigra pars reticulata GABAergic neuron activity by hydrogen peroxide via flufenamic acid-sensitive channels and KATP channels

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    Christian R Lee

    2011-04-01

    Full Text Available Substantia nigra pars reticulata (SNr GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2, a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid, implicating transient receptor potential (TRP channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of flufenamic acid revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea pig, with additional modulation via KATP channels to regulate SNr output.

  10. Neuromelanin-related contrast in the substantia nigra semiquantitatively evaluated by magnetic resonance imaging at 3T. Comparison between normal aging and Parkinson disease

    International Nuclear Information System (INIS)

    Tanaka, Makoto; Aihara, Yuko; Ikeda, Sachie; Aihara, Yoshiaki

    2011-01-01

    Fast spin-echo (FSE) T 1 -weighted magnetic resonance imaging (MRI) at 3T, which was optimized to detect neuromelanin-related contrast (NRC), was applied to quantitative estimation of signal alterations in the substantia nigra pars compacta (SNc) of 72 normal volunteers and 59 patients with Parkinson disease (PD). We examined relationship between NRC in SNc and clinical parameters. The NRC showed significant positive correlation with normal aging and was slightly but significantly higher in women than in men. Significant reduction in the NRC was found in PD as compared with 59 age- and sex-matched normal volunteers. The NRC in PD was negatively and significantly correlated with duration of illness and disease severity assessed by unified Parkinoson's disease rating scale (UPDRS) and Hoehn and Yahr stage. Significant reduction of the NRC was demonstrated in patients with visual hallucinations as compare with patients without the symptoms. Rapid eye movement (REM) sleep behavior disorder also contributed reduction of NRC although it did more mildly than visual hallucination. Anosmia or hyposmia had no statistical relationship with the amount of NRC in PD. The overall visual inspection indicated that the reduction of the NRC in PD should start at the ventrolateral portion of SNc and advance medially. Additionally, we studied dementia with Lewy body disease (DLB). The NRC was reduced more significantly in DLB patients with PD symptoms than in those without them who also showed a significant reduction compared with normal controls. Quantification and distribution of the NRC obtained by 3T MRI was well correlated with pathological findings reported previously and clinical parameters in this study. Visualization and quantification of the NRC provide some parts of clinical and diagnostic information about pathologic condition of SNc. (author)

  11. Ultra high-field SWI of the substantia nigra at 7T: reliability and consistency of the swallow-tail sign.

    Science.gov (United States)

    Schmidt, Manuel A; Engelhorn, Tobias; Marxreiter, Franz; Winkler, Juergen; Lang, Stefan; Kloska, Stephan; Goelitz, Philipp; Doerfler, Arnd

    2017-10-26

    The loss of the swallow-tail sign of the substantia nigra has been proposed for diagnosis of Parkinson's disease. Aim was to evaluate, if the sign occurs consistently in healthy subjects and if it can be reliably detected with high-resolution 7T susceptibility weighted imaging (SWI). Thirteen healthy adults received SWI at 7T. 3 neuroradiologists, who were blinded to patients' diagnosis, independently classified subjects regarding the swallow-tail sign to be present or absent. Accuracy, positive and negative predictive values (PPV and NPV) as well as inter- and intra-rater reliability and internal consistency were analyzed. The sign could be detected in 81% of the cases in consensus reading. Accuracy to detect the sign compared to the consensus was 100, 77 and 96% for the three readers with PPV reader 1/2/3 = 1/0.45/0.83 and NPV = 1/1/1. Inter-rater reliability was excellent (inter-class correlation coefficient = 0.844, alpha = 0.871). Intra-rater reliability was good to excellent (reader 1 R/L = 0.625/0.786; reader 2 = 0.7/0.64; reader 3 = 0.9/1). The swallow-tail sign can be reliably detected. However, our data suggest its occurrence is not consistent in healthy subjects. It may be possible that one reason is an individually variable molecular organization of nigrosome 1 so that it does not return a uniform signal in SWI.

  12. Regulation of Substantia Nigra Pars Reticulata GABAergic Neuron Activity by H2O2 via Flufenamic Acid-Sensitive Channels and KATP Channels

    Science.gov (United States)

    Lee, Christian R.; Witkovsky, Paul; Rice, Margaret E.

    2011-01-01

    Substantia nigra pars reticulata (SNr) GABAergic neurons are key output neurons of the basal ganglia. Given the role of these neurons in motor control, it is important to understand factors that regulate their firing rate and pattern. One potential regulator is hydrogen peroxide (H2O2), a reactive oxygen species that is increasingly recognized as a neuromodulator. We used whole-cell current clamp recordings of SNr GABAergic neurons in guinea-pig midbrain slices to determine how H2O2 affects the activity of these neurons and to explore the classes of ion channels underlying those effects. Elevation of H2O2 levels caused an increase in the spontaneous firing rate of SNr GABAergic neurons, whether by application of exogenous H2O2 or amplification of endogenous H2O2 through inhibition of glutathione peroxidase with mercaptosuccinate. This effect was reversed by flufenamic acid (FFA), implicating transient receptor potential (TRP) channels. Conversely, depletion of endogenous H2O2 by catalase, a peroxidase enzyme, decreased spontaneous firing rate and firing precision of SNr neurons, demonstrating tonic control of firing rate by H2O2. Elevation of H2O2 in the presence of FFA revealed an inhibition of tonic firing that was prevented by blockade of ATP-sensitive K+ (KATP) channels with glibenclamide. In contrast to guinea-pig SNr neurons, the dominant effect of H2O2 elevation in mouse SNr GABAergic neurons was hyperpolarization, indicating a species difference in H2O2-dependent regulation. Thus, H2O2 is an endogenous modulator of SNr GABAergic neurons, acting primarily through presumed TRP channels in guinea-pig SNr, with additional modulation via KATP channels to regulate SNr output. PMID:21503158

  13. Sustained effects of neonatal systemic lipopolysaccharide on IL-1β and Nrf2 in adult rat substantia nigra are partly normalized by a Spirulina enriched diet

    Science.gov (United States)

    Patil, Jaspal; Matte, Ashok; Nissbrandt, Hans; Mallard, Carina; Sandberg, Mats

    2016-01-01

    Background/Aim Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson’s disease in adults. We studied, prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin 1 beta (IL-1β), the antioxidant regulators nuclear factor-erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in rat SN. Method and Results Five-day old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1β was significantly increased in parallel with decreases in mRNAs of the rate limiting catalytic subunit of glutathione synthesis, γglutamylcysteine ligas (γGCLC), Nrf2 and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLC and Nrf2 were decreased while IL-1β protein was significantly increased. These LPS-induced long term changes were correlated with a decrease in phosphorylated AKT (pAKT) and phosphorylated-inactive GSK3β (pGSK3β). In another set of experiment, a Spirulina (0.1%) containing diet was given to lactating mothers 24 h before LPS treatment of the pups. The Spirulina supplemented diet decreased IL-1β protein expression in SN and elevated the mRNA level of the rate limiting catalytic subunit of glutathione synthesis, γglutamylcysteine ligas (γGCLC), Nrf2 protein, PGC-1α protein and pAKT. Conclusion Early life infection can negatively affect Nrf2, pAKT and pGSK3β for a long time in SN. A diet enriched in antioxidant and anti-inflammatory phytochemicals can partly restore some but not all the effects on the antioxidant defense, possibly via normalizing effects on pAKT. PMID:27931028

  14. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

    International Nuclear Information System (INIS)

    Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

    1997-01-01

    The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. THE EFFECT OF BETA GLUCAN OF SACCHAROMYCES CEREVISAE ON THE INCREASE OF THE NUMBER OF BRAIN CELLS IN SUBSTANTIA NIGRA BRAIN OF PARKINSON’S WISTAR STRAIN RAT (RATTUS NORVEGICUS MODEL INDUCED WITH ROTENONE

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    Masruroh Rahayu

    2015-01-01

    Full Text Available ackground and aims. One of many neurodegenerative diseases afflicting the elderly is Parkinson. Beta glucan from Saccharomyces cerevisae is very potential to be used as a regenerative therapy of Parkinson's disease. Beta glucan can increase the mobilization of hematopoietic stem cells (HSCs from the bone marrow into the damaged tissues. Hematopoietic stem cells (HSCs which have been mobilized can regenerate and differentiate into brain cells so that the symptoms of Parkinson would be reduced. This research aims to find out the effects of the addition of Saccharomyces cerevisae toward the number of brain cells in substantia nigra Parkinson’s rat model. Method. The research was experimental in vivo using the draft of randomized post test only controlled group design. There were five groups that become the sample in this research with 5 rats for each group, i.e. negative control group, positive control group, Treatment Group 1, 2 and 3 (Rotenone + Saccharomyces cerevisae 18 mg/kgBB, 36 mg/kgBB, 72 mg/kgBBfor 4 weeks. Variable measured in this study was the number of brain cells in substantia nigra. The results of this study showed that Treatment Group 3 (72 mg/kgBB was a group with the largest number of brain cells than the other treatment groups. Statistical data obtained showed that the average number of brain cells in negative control group was 192.00 cells; positive control amounted to 116.80 cells; Treatment 1 amounted to 135.40 cells; Treatment 2 amounted to 140.80 cells; and Treatment 3 amounted to 161.80 cells. Result. The result of ANOVA test showed a significant difference between groups (p< 0.05, while the correlation test result indicated a strong correlation between the dose of Saccharomyces cerevisae and the number of substantia nigra of rat’s brain cells (r = 0,818. Conclusion. From this research, it can be concluded that the addition of Saccharomyces cerevisae with a dose of 18mg/kgBB, 36mg/kgBBdan 72 mg/kgBB is able to increase

  16. Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

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    Hei, Ming-Yan; Luo, Ya-Li; Zhang, Xiao-Chun; Liu, Hong; Gao, Ru; Wu, Jing-Jiang [Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha, Hunan (China)

    2011-12-09

    Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O{sub 2}/92% N{sub 2}) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

  17. Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

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    Hei Ming-Yan

    2012-01-01

    Full Text Available Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI, and severe HI groups (N = 10 in each group at each time on postnatal day 7 (P7 to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH in the substantia nigra (SN. The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2 for 90 and 150 min, respectively. The elevated plus-maze (EPM test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05. The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2% and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05. The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

  18. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

    International Nuclear Information System (INIS)

    Thong, P.S.P.; Watt, F.; Ponraj, D.; Leong, S.K.; He, Y.; Lee, T.K.Y.

    1999-01-01

    Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN. This

  19. Changes in /sup 3/H-substance P receptor binding in the rat brain after kainic acid lesion of the corpus striatum

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    Mantyh, P.W.; Hunt, S.P.

    1986-06-01

    Previous studies have indicated that the substantia nigra contains the highest concentration of substance P-like immunoreactivity (SPLI) in the brain. Paradoxically, it also appears to contain one of the lowest concentrations of substance P receptors in the brain. One possibility is that the massive amount of SPLI blocks the binding of the radioligand to the substance P receptor and/or down-regulates the number of substance P receptors present in this structure. Since greater than 95% of the SPLI within the substantia nigra originates from the corpus striatum, we have lesioned this area and measured the changes in substance P receptor concentration in the substantia nigra and other corpus striatal projection areas. A semiquantitative autoradiographic technique for measuring the binding of /sup 3/H-substance P to substance P receptors was used in conjunction with tritium-sensitive film. 3H-substance P binding was measured in both the corpus striatum and its projection areas after kainic acid lesion of the corpus striatum. At either 4 or 21 d after the lesion there was approximately a 90% loss of substance P receptors in the rostral striatum, a 74% loss in the globus pallidus, a 57% increase in receptor number in lamina I and II of the ipsilateral somatosensory cortex, and no apparent change in the number of receptors in the substantia nigra pars reticulata, superior colliculus, and central gray. These findings suggest that the low concentration of substance P receptors found within the substantia nigra is not due the massive SPLI innervation, since removal of greater than 95% of the SPLI had no measurable effect on the concentration of substance P receptors.

  20. Noradrenergic lesion of the locus coeruleus increases apomorphine-induced circling behavior and the firing activity of substantia nigra pars reticulata neurons in a rat model of Parkinson's disease.

    Science.gov (United States)

    Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen Hua; Hui, Yan Ping; Chen, Li; Wu, Zhong Heng; Li, Qiang

    2010-01-15

    The role of noradrenergic depletion of the locus coeruleus (LC) in the pathophysiology of Parkinson's disease (PD) is still unclear. In the present study, apomorphine-induced circling behavior and extracellular firing activity of substantia nigra pars reticulata (SNr) neurons were examined in rats with unilateral 6-hydroxydopamine lesions of the LC, substantia nigra pars compacta (SNc) and with combined SNc and LC lesions. A moderate contralateral circling was observed in rats with LC lesions after apomorphine. Moreover, the circling behavior was obviously increased by further lesions of LC in SNc-lesioned rats. Extracellular recordings indicated that the firing rate of SNr neurons increased significantly and the firing pattern of these neurons also changed towards more irregular and bursty after SNc lesioning as compared to sham-lesioned rats, while the firing rate and pattern were unaffected in rats with simple lesions of the LC. However, the firing rate of SNr neurons in rats with combined LC and SNc lesions increased significantly when compared to that of rats with simple lesions of the SNc, although the firing pattern was not altered. Furthermore, SNc lesions in rats increased the firing rate of SNr neurons with irregular firing pattern, and additional LC lesions in SNc-lesioned rats increased the firing rate of SNr neurons with regular and irregular firing pattern. These results indicate that lesions of the LC intensify apomorphine-induced circling behavior and lead to a further hyperactivity of SNr neurons in a rat model of PD, suggesting that LC-noradrenergic system is involved in the motor dysfunction of PD. Copyright 2009 Elsevier B.V. All rights reserved.

  1. A comparison of substantia nigra T1 hyperintensity in Parkinson's disease dementia, Alzheimer's disease and age-matched controls: Volumetric analysis of neuromelanin imaging

    International Nuclear Information System (INIS)

    Moon, Won Jin; Park, Ju Yeon; Yun, Won Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Hee Jin; Han, Seol Heui; Kwak, Ki Chang; Lee, Jong Min

    2016-01-01

    Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases

  2. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

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    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  3. A comparison of substantia nigra T1 hyperintensity in Parkinson's disease dementia, Alzheimer's disease and age-matched controls: Volumetric analysis of neuromelanin imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Park, Ju Yeon; Yun, Won Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Hee Jin; Han, Seol Heui [Konkuk University School of Medicine, Seoul (Korea, Republic of); Kwak, Ki Chang; Lee, Jong Min [Dept. of Biomedical Engineering, Hanyang University, Seoul (Korea, Republic of)

    2016-09-15

    Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases.

  4. Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease

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    Biggs Christopher S

    2007-07-01

    Full Text Available Abstract We have recently observed that the corticotrophin releasing hormone (CRF related peptide urocortin (UCN reverses key features of nigrostriatal damage in the hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether similar effects are also evident in the lipopolysaccaride (LPS neuroinflammatory paradigm of Parkinson's disease (PD. To do this we have measured restoration of normal motor behaviour, retention of nigral dopamine (DA and also tyrosine hydroxylase (TH activity. Fourteen days following intranigral injections of LPS and UCN, rats showed only modest circling after DA receptor stimulation with apomorphine, in contrast to those given LPS and vehicle where circling was pronounced. In separate experiments, rats received UCN seven days following LPS, and here apomorphine challenge caused near identical circling intensity to those that received LPS and UCN concomitantly. In a similar and consistent manner with the preservation of motor function, UCN 'protected' the nigra from both DA depletion and loss of TH activity, indicating preservation of DA cells. The effects of UCN were antagonised by the non-selective CRF receptor antagonist α-helical CRF and were not replicated by the selective CRF2 ligand UCN III. This suggests that UCN is acting via CRF1 receptors, which have been shown to be anti-inflammatory in the periphery. Our data therefore indicate that UCN is capable of maintaining adequate nigrostriatal function in vivo, via CRF1 receptors following a neuro-inflammatory challenge. This has potential therapeutic implications in PD.

  5. Prolonged Dysfunction of Astrocytes and Activation of Microglia Accelerate Degeneration of Dopaminergic Neurons in the Rat Substantia Nigra and Block Compensation of Early Motor Dysfunction Induced by 6-OHDA.

    Science.gov (United States)

    Kuter, Katarzyna; Olech, Łukasz; Głowacka, Urszula

    2018-04-01

    Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is the underlying cause of Parkinson's disease (PD). The disease in early stages is difficult to diagnose, because behavioral deficits are masked by compensatory processes. Astrocytic and microglial pathology precedes motor symptoms. Besides supportive functions of astrocytes in the brain, their role in PD is unrecognized. Prolonged dysfunction of astrocytes could increase the vulnerability of dopaminergic neurons and advance their degeneration during aging. The aim of our studies was to find out whether prolonged dysfunction of astrocytes in the SN is deleterious for neuronal functioning and if it influences their survival after toxic insult or changes the compensatory potential of the remaining neurons. In Wistar rat model, we induced activation, prolonged dysfunction, and death of astrocytes by chronic infusion of fluorocitrate (FC) into the SN, without causing dopaminergic neuron degeneration. Strongly enhanced dopamine turnover in the SN after 7 days of FC infusion was induced probably by microglia activated in response to astrocyte stress. The FC effect was reversible, and astrocyte pool was replenished 3 weeks after the end of infusion. Importantly, the prolonged astrocyte dysfunction and microglia activation accelerated degeneration of dopaminergic neurons induced by 6-hydroxydopamine and blocked the behavioral compensation normally observed after moderate neurodegeneration. Impaired astrocyte functioning, activation of microglia, diminishing compensatory capability of the dopaminergic system, and increasing neuronal vulnerability to external insults could be the underlying causes of PD. This animal model of prolonged astrocyte dysfunction can be useful for in vivo studies of glia-microglia-neuron interaction.

  6. Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

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    Noël F.

    2000-01-01

    Full Text Available Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

  7. Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

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    Haiyan Jiang

    2018-05-01

    Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

  8. Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.

    Science.gov (United States)

    Spampinato, U; Esposito, E; Samanin, R

    1985-09-01

    The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.

  9. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon.

    Science.gov (United States)

    da Silva, Juliana Almeida; Biagioni, Audrey Francisco; Almada, Rafael Carvalho; de Souza Crippa, José Alexandre; Cecílio Hallak, Jaime Eduardo; Zuardi, Antônio Waldo; Coimbra, Norberto Cysne

    2015-07-05

    Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum.

    Science.gov (United States)

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Fernandes, Henrique Schaan; Teixeira, Alexsander Alves; Guasselli, Marcelo Otavio Rodrigues; Agani, Crepin Aziz Jose O; Souza, Natália Cabral; Grings, Mateus; Leipnitz, Guilhian; Gomes, Henrique Mautone; de Bittencourt Pasquali, Matheus Augusto; Dunkley, Peter R; Dickson, Phillip W; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-05-01

    Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50μg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1β) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1β in CSF. In striatum, RAGE antibody inhibited increases in IL-1β, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease.

    Science.gov (United States)

    López Hernández, N; García Escrivá, A; Shalabi Benavent, M

    2015-10-01

    Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  13. 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.

  14. Transcranial Sonographic Alterations of Substantia Nigra and Third Ventricle in Parkinson's Disease with or without Dementia

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    Zhi-Fen Dong

    2017-01-01

    Conclusions: Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.

  15. Calcium Homeostatasis and Mitochondrial Dysfunction in Dopaminergic Neurons of the Substantia Nigra

    Science.gov (United States)

    2010-03-01

    and Hind III fragment containing TH promoter/MTS-roGFP/polyadenylation sequences was purified by 0.8% agarose gel electrophoresis , and eluted with...submitted): Chan et al. (2009) pdf attached Guzman et al., (2009) pdf attached Guzman et al., (2010 in revision) pdf attached Surmeier et al. (2010... pdf attached Calcium homeostasis, selective vulnerability and Parkinson’s disease C. Savio Chan*, Tracy S. Gertler* and D. James Surmeier

  16. Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson's disease.

    Science.gov (United States)

    Al-Jarrah, Muhammed; Obaidat, Heyam; Bataineh, Ziad; Walton, Lori; Al-Khateeb, Ahed

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder, caused by the gradual loss of cells in substantia nigra. Nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of nervous system. The aims of this study are: 1) To investigate the expression of the inducible form of NO (iNOS), and compare it to neuronal nitric oxide (nNOS) in the brain of a chronic mouse model of PD and 2) To study the effect of endurance exercise training on the expression of these markers. Mouse models of PD were obtained using 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Forty C57BL /6 albino mice were randomly divided into four groups: sedentary control (SC, N = 10), exercise control (EC, N = 10), sedentary PD (SPD, N = 10), exercise PD (EPD, N = 10). At the end of training program, nNOS and iNOS were evaluated in the striatum in all animal groups using immunohistochemistry. nNOS showed significant increases in striatum (ST) of SPD mice compared to SC mice (P > 0.03). There was also decreased expression of nNOS in EC group compared to SC mice, but this decrease was not significant (P > 0.8). Exercise training significantly decreased the level of nNOS in the EPD compared to SPD, (P > 0.04). Although, iNOS expression followed almost the same trend as nNOS, but exercise training did not significantly decrease the expression of iNOS in both EC and EPD groups, P > 0.2 and 0.3 respectively. The data from this study suggests that 4 weeks of treadmill exercise has a positive impact on the expression of nNOS and iNOS in the striatum of a PD model. This might clear in part the pathogenicity of the diseases and the positive impact of training on PD.

  17. Basketball training increases striatum volume.

    Science.gov (United States)

    Park, In Sung; Lee, Kea Joo; Han, Jong Woo; Lee, Nam Joon; Lee, Won Teak; Park, Kyung Ah; Rhyu, Im Joo

    2011-02-01

    The striatum is associated with the learning and retention of motor skills. Several studies have shown that motor learning induces neuronal changes in the striatum. We investigated whether macroscopic change in striatum volume occurs in a segment of the human population who learned basketball-related motor skills and practiced them throughout their entire athletic life. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players and healthy controls, and striatum volumes were compared based on basketball proficiency, region and side. We identified morphological enlargement in the striatum of basketball players in comparison with controls. Our results suggest that continued practice and repetitive performance of basketball-related motor skills may induce plastic structural changes in the human striatum. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Protective Effects of Water Extract of Morus Nigra L. on 6-Hydroxydopamine Induced Parkinson’s Disease in Male Rats

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    Seyed Ali Ziai

    2018-01-01

    Full Text Available Background: Parkinson’s disease (PD is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is unknown, but major biochemical processes such as oxidative stress is largely described. Angiotensin II activates NADPH depending oxidases and produce superoxides formation. Morus nigra L. extract is an Angiotensin Converting Enzyme (ACE inhibitor and tested for anti-Parkinsonism effects by biochemical and behavioral evaluations.Materials and Methods: In total 48 Male Wistar rats weighting 200-250 g were divided into 4 groups: (1 Sham (normal saline was injected in the left SNC, (2 Neurotoxin (injection of 6-hydroxydopamine into left SNC, (3 Morus nigra L. aqueous extract and (4 captopril. Morus nigra (10 mg/kg and captopril (5 mg/kg were daily-injected i.p. from 6 days before neurotoxin injection, until one day after 6-hydroxydopamine injection. Muscle stiffness and apomorphine test were assessed in 6 rats of any groups after two weeks. Protein oxidation, lipid peroxidation and ACE activity were assessed in brains of 6 rats of each group after 24 hours.Results: Rotation test with apomorphine, Rigidity with Murprogo’s test, and lipid peroxidation in sham, captopril and Morus nigra groups were significantly lower than neurotoxin group. Protein oxidation in Morus nigra group was significantly lower than neurotoxin group. Brain ACE activity in neurotoxin, captopril and Morus nigra groups were inhibited.Conclusion: Morus nigra L. extract had protective effects on neuronal oxidation and death and improved signs of PD possibly by ACE inhibition.

  19. Histamine and the striatum.

    Science.gov (United States)

    Bolam, J Paul; Ellender, Tommas J

    2016-07-01

    The neuromodulator histamine is released throughout the brain during periods of wakefulness. Combined with an abundant expression of histamine receptors, this suggests potential widespread histaminergic control of neural circuit activity. However, the effect of histamine on many of these circuits is unknown. In this review we will discuss recent evidence for histaminergic modulation of the basal ganglia circuitry, and specifically its main input nucleus; the striatum. Furthermore, we will discuss recent findings of histaminergic dysfunction in several basal ganglia disorders, including in Parkinson's disease and most prominently, in Tourette's syndrome, which has led to a resurgence of interest in this neuromodulator. Combined, these recent observations not only suggest a central role for histamine in modulating basal ganglia activity and behaviour, but also as a possible target in treating basal ganglia disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Effects of [Des-Tyr1]-γ-endorphin and α-endorphin on substantia nigra self-stimulation

    NARCIS (Netherlands)

    Dorsa, D.M.; Ree, J.M. van; Wied, D. de

    The β-lipotropin fragments, [des-Tyr1]-γ-endorphin (DTγE, β-LPH62–77) and α-endorphin (β-LPH61–76) affect self-stimulating behavior associated with electrical stimulation of neurons of the ventral tegmentum area of rats in an opposite way. Subcutaneous administration of DTγE (5 and 25 μg) attenuated

  1. Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro

    DEFF Research Database (Denmark)

    Rice, M E; Richards, C D; Nedergaard, S

    1994-01-01

    electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high...

  2. Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

    Science.gov (United States)

    Hu, Tao; Liu, Nana; Lv, Minhua; Ma, Longxian; Peng, Huizhen; Peng, Sicong

    2016-01-01

    BACKGROUND: Lidocaine, which blocks voltage-gated sodium channels, is widely used in surgical anesthesia and pain management. Recently, it has been proposed that the hyperpolarization-activated cyclic nucleotide (HCN) channel is one of the other novel targets of lidocaine. Substantia gelatinosa in the spinal dorsal horn, which plays key roles in modulating nociceptive information from primary afferents, comprises heterogeneous interneurons that can be electrophysiologically categorized by firing pattern. Our previous study demonstrated that a substantial proportion of substantia gelatinosa neurons reveal the presence of HCN current (Ih); however, the roles of lidocaine and HCN channel expression in different types of substantia gelatinosa neurons remain unclear. METHODS: By using the whole-cell patch-clamp technique, we investigated the effect of lidocaine on Ih in rat substantia gelatinosa neurons of acute dissociated spinal cord slices. RESULTS: We found that lidocaine rapidly decreased the peak Ih amplitude with an IC50 of 80 μM. The inhibition rate on Ih was not significantly different with a second application of lidocaine in the same neuron. Tetrodotoxin, a sodium channel blocker, did not affect lidocaine’s effect on Ih. In addition, lidocaine shifted the half-activation potential of Ih from −109.7 to −114.9 mV and slowed activation. Moreover, the reversal potential of Ih was shifted by −7.5 mV by lidocaine. In the current clamp, lidocaine decreased the resting membrane potential, increased membrane resistance, delayed rebound depolarization latency, and reduced the rebound spike frequency. We further found that approximately 58% of substantia gelatinosa neurons examined expressed Ih, in which most of them were tonically firing. CONCLUSIONS: Our studies demonstrate that lidocaine strongly inhibits Ih in a reversible and concentration-dependent manner in substantia gelatinosa neurons, independent of tetrodotoxin-sensitive sodium channels. Thus, our

  3. Adventitious shoot regeneration of Fraxinus nigra Marsh

    Science.gov (United States)

    Rochelle R. Beasley; Paula M. Pijut

    2010-01-01

    Fraxinus nigra Marsh. (black ash) is a native ash species occurring in Newfoundland west to Manitoba and south to Iowa, Illinois, West Virginia, and Virginia. Although it is not a commercially important species, it has significant ethnobotanical importance to Native American tribes of the eastern United States.

  4. Dematosis Papulosa Nigra | Shamad | Sudanese Journal of ...

    African Journals Online (AJOL)

    ... hyperpigmented, smoothsurfaced, round or filiform papules that measure 1-5 mm in diameter; appearing usually on the face, but sometimes on the neck or upper trunk. A liturature review is presented herein this paper. Keywords: Dermatosis papulosa nigra, Pilosebaceous folicles. Sudanese Journal of Dermatology Vol.

  5. Antioxidant properties of Sambucus nigra flower extracts.

    OpenAIRE

    Štěpánová, Zuzana

    2013-01-01

    1. Abstract Purpose of this thesis was to prove and determine antioxidant activity of flower extracts from black elder (Sambucus nigra L.) and compile summary of their content substances and effects. Sambuci flos is often used in natural therapy and food industry. The main content substances are flavonoids, phenolic acids, triterpenoids, further are contained in flowers sterols, mucilage, essential oils, tannins. Flavonoids are the most significant, specifically rutin and kvercetin, because t...

  6. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    OpenAIRE

    Valentin Bhimba B; V Vinod; M Cindhu Beulah

    2011-01-01

    Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra) collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites...

  7. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    Directory of Open Access Journals (Sweden)

    Valentin Bhimba B

    2011-12-01

    Full Text Available Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites were characterized by gas chromatography-mass spectrometry (GC-MS analysis. Conclusions: Based on the present study, it can be inferred that the bioassay guided fractionation and purification of D. nigra may come up with potent bioactive drug.

  8. [Compartmentalized organization of human corpus striatum].

    Science.gov (United States)

    Prensa, L; Parent, A; Giménez-Amaya, J M

    The compartmentalization of the human striatum was first established thanks to the pioneer work of Graybiel and Ragsdale in 1978. These authors described in the human striatum, as well as in the cats and primates, zones poorly stained for the enzyme acetylcholinesterase, which they termed striosomes, that lie in more intensely stained matrix. The striosome/matrix subdivision of the striatum is supported by the distribution of a wide variety of transmitter-related substances and by the organization of striatal afferent and efferent connections. The results of many studies performed in different species in the last twenty years have indicated that the chemical heterogeneity of striatum is more complex than the simple subdivision into striosomes and matrix compartments. Thus, a further subdivisions of the dual striosome/matrix system has been proposed on the basis of the results of a huge amount of works combining tract tracing methods with histochemical techniques. The matrix has been demonstrated to be heterogeneous by containing numerous functional modules that were termed matrisomes. Furthermore, the most recent study of the distribution of a wide variety of neurochemical markers in the striosomal compartment of the human striatum, has revealed that the striosomes are themselves heterogeneous, being composed of a central core and a peripheral region. Since it is now twenty years from the first description of the striosome/matrix organization of the striatum, in this review we intend to summarize the major finding regarding the compartmental organization of this subcortical structure that have been obtained during this period of time.

  9. Tolerance of Brassica nigra to Pieris brassicae herbivory

    NARCIS (Netherlands)

    Blatt, S.E.; Smallegange, R.C.; Hess, L.; Harvey, J.A.; Dicke, M.; Loon, van J.J.A.

    2008-01-01

    Black mustard, Brassica nigra (L.) Koch, is a wild annual species found throughout Europe and fed on by larvae of the large cabbage-white butterfly, Pieris brassicae L. We examined the impact of herbivory from P. brassicae, a gregarious herbivore, on B. nigra grown from wild seed collected locally.

  10. Tolerence of Braccica nigra to Pieris brassicae herbivory

    NARCIS (Netherlands)

    Blatt, S.E.; Smallegange, R.C.; Hess, L.; Harvey, J.A.; Dicke, D.; van Loon, J.J.A.

    2008-01-01

    Black mustard, Brassica nigra (L.) Koch, is a wild annual species found throughout Europe and fed on by larvae of the large cabbage-white butterfly, Pieris brassicae L. We examined the impact of herbivory from P. brassicae, a gregarious herbivore, on B. nigra grown from wild seed collected locally.

  11. Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

    NARCIS (Netherlands)

    Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.

    2001-01-01

    Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

  12. Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

    International Nuclear Information System (INIS)

    Ceballos, M.L. de; Boyce, S.; Taylor, M.; Jenner, P.; Marsden, C.D.

    1987-01-01

    Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens

  13. Encoding by synchronization in the primate striatum.

    Science.gov (United States)

    Adler, Avital; Finkes, Inna; Katabi, Shiran; Prut, Yifat; Bergman, Hagai

    2013-03-13

    Information is encoded in the nervous system through the discharge and synchronization of single neurons. The striatum, the input stage of the basal ganglia, is divided into three territories: the putamen, the caudate, and the ventral striatum, all of which converge onto the same motor pathway. This parallel organization suggests that there are multiple and competing systems in the basal ganglia network controlling behavior. To explore which mechanism(s) enables the different striatal domains to encode behavioral events and to control behavior, we compared the neural activity of phasically active neurons [medium spiny neurons (MSNs), presumed projection neurons] and tonically active neurons (presumed cholinergic interneurons) across striatal territories from monkeys during the performance of a well practiced task. Although neurons in all striatal territories displayed similar spontaneous discharge properties and similar temporal modulations of their discharge rates to the behavioral events, their correlation structure was profoundly different. The distributions of signal and noise correlation of pairs of putamen MSNs were strongly shifted toward positive correlations and these two measures were correlated. In contrast, MSN pairs in the caudate and ventral striatum displayed symmetrical, near-zero signal and noise correlation distributions. Furthermore, only putamen MSN pairs displayed different noise correlation dynamics to rewarding versus neutral/aversive cues. Similarly, the noise correlation between tonically active neuron pairs was stronger in the putamen than in the caudate. We suggest that the level of synchronization of the neuronal activity and its temporal dynamics differentiate the striatal territories and may thus account for the different roles that striatal domains play in behavioral control.

  14. Regeneration of plants from Fraxinus nigra Marsh. hypocotyls

    Science.gov (United States)

    Rochelle R. Beasley; Paula M. Pijut

    2013-01-01

    Fraxinus nigra Marsh. (black ash) is a native North American hardwood tree species that is ecologically important and has ethnobotanical significance to American Indian communities of the eastern United States. Black ash has immature embryos at seed set, combined with complex stratification requirements, making natural regeneration difficult. This,...

  15. Genetic homogeneity in Juglans nigra(Juglanaceae) at nuclear microsatellites

    Science.gov (United States)

    Erin R. Victory; Jeffrey C. Glaubitz; Olin E., Jr. Rhodes; Keith E. Woeste

    2006-01-01

    Broad-scale studies of genetic structure and diversity are indicative of the recent evolutionary history of a species and are relevant to conservation efforts. We have estimated current levels of genetic diversity and population structure for black walnut (Juglans nigra L.), a highly valuable timber species, in the central hardwood region of the...

  16. Floristic diversity and vegetation analysis of Brassica nigra (L.) Koch ...

    African Journals Online (AJOL)

    The floristic composition and species diversity of Brassica nigra communities were investigated in Beni Suef Governorate, Egypt. In 46 stands, a total of 49 species belonging to 42 genera and 18 families were recorded. Vegetation classification and ordination distinguished seven groups: two in reclaimed land only, three ...

  17. utilization of tortoise (chelonoides nigra, quoy and gaimard, 1824)

    African Journals Online (AJOL)

    Tersor

    revealed that Chelonoidis nigra is popular in the study area and it is mostly utilized as food and therefore hunted for .... Table 1b: Respondents ways of utilization of tortoise in the study area. Variable. Frequency (F). Percentage %. For food. 98. 79.03. For sale. 21. 16.94. For food / sale. 5. 4.03 ..... A dictionary of the economic.

  18. Urethritis due to corynebacterium striatum: An emerging germ.

    Science.gov (United States)

    Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

    2015-01-01

    Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

  19. Striatum on the anxiety map: Small detours into adolescence.

    Science.gov (United States)

    Lago, Tiffany; Davis, Andrew; Grillon, Christian; Ernst, Monique

    2017-01-01

    Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. This article is part of a Special Issue entitled SI: Adolescent plasticity. Published by Elsevier B.V.

  20. Cannabis use and abuse correlates in a homogeneous South ...

    African Journals Online (AJOL)

    2009-03-01

    Mar 1, 2009 ... Vahl proposed that tetrahydrocannabinol (THC) protects against movement disorders by stimulating release of dopamine from dopaminergic projections from the substantia nigra ending in the striatum.29 It is known that deficiencies of this pathway may cause movement disorders. Possible limitations of this ...

  1. Computational evaluation of small molecule inhibitors of RGS4 to ...

    African Journals Online (AJOL)

    Parkinson's disease is a neurodegenerative disease which is the result of the degradation of the dopaminergic neurons in the substantia nigra pars compacta, leading to a disregulation of thalamocortical circuits. Traditional treatment involves the use of levodopa which increases the dopamine level in the striatum. There is a ...

  2. Role of nigro-neostriatal dopaminergic fibers in compulsive gnawing behavior in rats

    NARCIS (Netherlands)

    Smelik, P.G.; Ernst, A.M.

    Implantation of crystalline physostigmine in the substantia nigra in rats resulted in compulsive gnawing behavior, which has also been found to result from dopa or apomorphine implantation in the neo-striatum. Atropine pretreatment prevented the effect of physostigmine implants. It is concluded

  3. Effect of acute whole-body neutron gamma irradiation on the dopamine neuronal uptake-sites

    International Nuclear Information System (INIS)

    Martin, C.; Mahfoudi, H.; Lambert, F.; Burckhart, M.F.; Fatome, M.

    1997-01-01

    The effects of (neutron-gamma) irradiation on the dopamine uptake sites distribution were investigated, using quantitative autoradiography. Brain ares examined are striatum, lateral septum, substantia nigra, gyrus dentatus, ventral tegmental area, interfascicular nu and antero-ventral thalamic nu. Three hours after exposure at the dose of 4 Gy, a decrease (- 33 %) of dopamine uptake sites was observed in the gyrus dentatus. (authors)

  4. Effect of acute whole-body neutron gamma irradiation on the dopamine neuronal uptake-sites; Effets d`une irradiation globale aigue a preponderance neutron sur le transporteur de capture neuronale de la dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Martin, C.; Mahfoudi, H.; Lambert, F.; Burckhart, M.F.; Fatome, M. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)

    1997-12-31

    The effects of (neutron-gamma) irradiation on the dopamine uptake sites distribution were investigated, using quantitative autoradiography. Brain ares examined are striatum, lateral septum, substantia nigra, gyrus dentatus, ventral tegmental area, interfascicular nu and antero-ventral thalamic nu. Three hours after exposure at the dose of 4 Gy, a decrease (- 33 %) of dopamine uptake sites was observed in the gyrus dentatus. (authors)

  5. Xenotransplantation in Parkinson's disease

    NARCIS (Netherlands)

    Koopmans, Jan

    2006-01-01

    Parkinson's disease is a neurodegenerative disorder characterised by loss of dopaminergic neurones in the substantia nigra pars compacta and subsequent shortage of dopamine in the striatum of the these patients causing the well known symptoms first described by James Parkinson in 1817. In this

  6. Pharmacognostical Investigations on Sambucus ebulus L. and Sambucus nigra L

    Directory of Open Access Journals (Sweden)

    Dr. A. R. Ghannadi

    1997-08-01

    Full Text Available Several species of the genus Sambucus have been used in treating symptoms of the common cold and some skin ailments. Four species of this plant are growing extensively in Iran. One of these species is S.ebulus. In this study, S. ebulus was examined botanically and phytochemicatly in comparison to S. nigra."nMorphological as well as microscopical characteristics of S. ebulus and S. nigra were examined. By means of TLC in comparison to authentic samples, Rutin, Hyperin. Apigenin and Chlorogenic acid were identified in these plants. By preparative TLC method, Rutin is isolated and then purified from these plants. The structure of Rutin was determined by the UV-Vis. Techniques in methanol and by addition of the shift reagents and hydrolysis. The quantitative determinations of fiavonoids in these plants were also performed by using an UV-Vis. Spectroscopy method.

  7. Dopamine release in ventral striatum of pathological gamblers losing money

    DEFF Research Database (Denmark)

    Linnet, J; Peterson, E; Doudet, D J

    2010-01-01

    Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

  8. Native valve endocarditis caused by an organism resembling Corynebacterium striatum.

    OpenAIRE

    Markowitz, S M; Coudron, P E

    1990-01-01

    An organism resembling Corynebacterium striatum was isolated from the blood of a patient with acute aortic valvular insufficiency and no history of valvular heart disease. At autopsy, histopathologic examination of the aortic valve revealed pleomorphic gram-positive bacilli and destruction of valvular tissue. Our isolate differed from other nondiphtherial corynebacteria, including the type strain of C. striatum (ATCC 6940), in its ability to reduce nitrite. Nitrite reduction may be useful for...

  9. High density of benzodiazepine binding sites in the substantia innominata of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Sarter, M.; Schneider, H.H.

    1988-07-01

    In order to study the neuronal basis of the pharmacological interactions between benzodiazepine receptor ligands and cortical cholinergic turnover, we examined the regional distribution of specific benzodiazepine binding sites using in vitro autoradiography. In the basal forebrain, the substantia innominata contained a high density of (/sup 3/H)lormetazepam (LMZ) binding sites (Bmax = 277 fmol/mg tissue; Kd = 0.55 nM). The label could be displaced by diazepam (IC50 = 100 nM), the benzodiazepine receptor antagonist beta-carboline ZK 93426 (45 nM) and the partial inverse agonist beta-carboline FG 7142 (540 nM). It is hypothesized that the amnesic effects of benzodiazepine receptor agonists are exerted through benzodiazepine receptors which are situated on cholinergic neurons in the substantia innominata and are involved in a tonic inhibition of cortical acetylcholine release. The benzodiazepine receptor antagonist ZK 93426 may exert its nootropic effects via benzodiazepine receptors in the substantia innominata and, consequently, by disinhibiting cortical acetylcholine release.

  10. Functional connectivity of the dorsal striatum in female musicians

    Directory of Open Access Journals (Sweden)

    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.

  11. Functional Connectivity of the Dorsal Striatum in Female Musicians.

    Science.gov (United States)

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    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 functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. 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, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective.

  12. Bioassay-Guided Isolation and Characterization of Wound Healer Compounds from Morus nigra L. (Moraceae)

    OpenAIRE

    Esra Küpeli Akkol; Ipek Süntar; Hikmet Keleş; Ekrem Sezik; Gülnur Gürler

    2015-01-01

    Leaves and fruits of Morus nigra L. (Moraceae) are used for the treatment of wounds especially mouth sore in Turkish traditional medicine. The present study was designed to investigate wound healing activity of M. nigra by using incision and excision wound models. Furthermore, anti-inflammatory activity was assessed by Whittle method. Lyophilized fruit extract (MNF) displayed significant wound healing activity, while aqueous leaf extract of M. nigra (MNL) did not. Through biological activity ...

  13. Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

    Directory of Open Access Journals (Sweden)

    Yan-Ling Yang

    Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

  14. Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

    Science.gov (United States)

    Stefan, V.

    2013-03-01

    A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

  15. Cholinergic interneurons are differentially distributed in the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2007-11-14

    The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons

  16. Stand structure and climate influence on the growth trends of a marginal forest population of Pinus nigra spp. nigra

    Directory of Open Access Journals (Sweden)

    Maurizio Marchi

    2015-12-01

    Full Text Available The Black pine of Villetta Barrea (Pinus nigra ssp. nigra var italica is a variety of the nigra subspecies. It is naturally distributed only in the Abruzzo Region, near the village of Villetta Barrea, with a rear-edge marginal population.  A dendrochronological sampling of the population was implemented with the aim of studying its stand structure and the most probable interactions between growth trends and climate. Mensurational data were used to characterize the stand and, furthermore, the general correlation function (CF and the moving correlation function (MCF, with a 30 years window, were used to assess the interrelation between the growth of the tree rings and the climate.The results indicated that the past forest management, mainly carried out with thinnings from below and selective cuttings, influenced the current structure of the forest (mean diameter but no differences in growth trends were detected within the population.The survey on Villetta Barrea Black pine showed a positive and statistically significant correlation between the ring-width and the average temperatures of the months of December (before the ring formation - t-1, February and March; but it also showed a negative correlation with the temperatures of July, September and October of the current year (t.Moreover, the analysis with moving correlation functions suggested that, in the last decades, the population has negatively reacted to very few climate factors and, in particular, to the changes in temperatures (both minimum and maximum temperatures. This is especially true for the shifts occurred in September, the year of the ring formation.

  17. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  18. The dorsal striatum and ventral striatum play different roles in the programming of social behaviour: a tribute to Lex Cools.

    Science.gov (United States)

    van den Bos, Ruud

    2015-02-01

    Early work by Lex Cools suggested that the caudate nucleus (dorsal striatum) plays a role in programming social behaviour: enhanced activity in the caudate nucleus increased the extent to which ongoing behaviour is controlled by the individual's own behaviour (internal control) rather than by that of its partners (external control). Interestingly, later studies by others have indicated that the ventral striatum plays a role in external rather than internal control. Here, I discuss the role of these different striatal areas - and the emotional (ventral striatum) and cognitive control (dorsal striatum) system in which they are embedded - in the organization of social behaviour in the context of locus of control. Following on from this discussion, I will pay particular attention to individual differences in social behaviour (individuals with more internal or external control), focusing on the role of dopamine, serotonin and the effects of stress-related challenges in relation to their different position in a dominance hierarchy. I will subsequently allude to potential psychological and behavioural problems in the social domain following on from these differences in locus of control ['social obliviousness' (dorsal stratum) and 'social impulsivity' (ventral striatum)]. In doing so, I provide as a tribute a historical account of the early research by Lex Cools.

  19. Hepatoprotective activity of aqueous methanolic extract of Morus nigra against paracetamol-induced hepatotoxicity in mice

    Directory of Open Access Journals (Sweden)

    Tauqeer Hussain Mallhi

    2014-03-01

    Full Text Available Morus nigra (Family Moraceae is traditionally used injaundice, diabetes, hypertension, cough, fever and cancer. The current study was conducted to determine hepatoprotective activity of aqueous methanolic extract of leaves of M. nigra. Two doses of 250 mg/kg p.o and 500 mg/kg p.o showed that extract of M. nigra produced significant (p<0.001 reduction in liver enzymes (ALT, AST, ALP and total bilirubin induced by paracetamol and the results are comparable to silymarin (p<0.001. Results were supported by histopathologi-cal investigations, phytochemical screening and detection of active consti-tuents by HPLC. The current study showed that aqueous methanolic extract of M. nigra possess hepatoprotective activity that might be due to quercetin, luteolin and isorhamnetin. It was concluded from this study that M. nigra has hepatoprotective activity against paracetamol induced liver injury in mice.

  20. Application of canonical discriminant analysis in differentiation of natural populations of Pinus nigra in Serbia based on terpene composition

    OpenAIRE

    Šarac, Z.; Bojović, S.; Nikolić, B.; Zlatković, B.; Marin, P.

    2014-01-01

    The canonical discriminant analysis (CDA) was performed in order to check the hypothesis of chemical separation infraspecific taxa of Pinus nigra J.F. Arnold (ssp. nigra, var. gocensis, ssp. pallasiana, and var. banatica) in Serbia based on variability of the needle terpenes. The CDA, which maximizes variations between a priori groups, showed division of seven native P. nigra populations into three groups, which belong to three taxonomically recognized taxa (ssp. nigra, ssp. pallasiana, and v...

  1. Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

    Science.gov (United States)

    Romeo, Stefania; Viaggi, Cristina; Di Camillo, Daniela; Willis, Allison W; Lozzi, Luca; Rocchi, Cristina; Capannolo, Marta; Aloisi, Gabriella; Vaglini, Francesca; Maccarone, Rita; Caleo, Matteo; Missale, Cristina; Racette, Brad A; Corsini, Giovanni U; Maggio, Roberto

    2013-01-01

    This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

  2. Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

    Science.gov (United States)

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

    2011-01-01

    Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

  3. Ebf1 controls early cell differentiation in the embryonic striatum.

    Science.gov (United States)

    Garel, S; Marín, F; Grosschedl, R; Charnay, P

    1999-12-01

    Ebf1/Olf-1 belongs to a small multigene family encoding closely related helix-loop-helix transcription factors, which have been proposed to play a role in neuronal differentiation. Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed. Ebf1 targeted disruption affects postmitotic cells that leave the subventricular zone (SVZ) en route to the mantle: they appear to be unable to downregulate genes normally restricted to the SVZ or to activate some mantle-specific genes. These downstream genes encode a variety of regulatory proteins including transcription factors and proteins involved in retinoid signalling as well as adhesion/guidance molecules. These early defects in the SVZ/mantle transition are followed by an increase in cell death, a dramatic reduction in size of the postnatal striatum and defects in navigation and fasciculation of thalamocortical fibres travelling through the striatum. Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon.

  4. Attention modulates the dorsal striatum response to love stimuli.

    Science.gov (United States)

    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.

  5. File list: Pol.Neu.50.AllAg.Corpus_Striatum [Chip-atlas[Archive

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  7. Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract

    OpenAIRE

    ANA LÚCIA B. ZENI; TATIANNE D. MOREIRA; ANA PAULA DALMAGRO; ANDERSON CAMARGO; LARISSA A. BINI; EDÉSIO L. SIMIONATTO; DILAMARA R. SCHARF

    2017-01-01

    ABSTRACT Morus nigra L. (Moraceae) is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN) showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively), as well as antiox...

  8. THE STUDY OF MORPHOLOGICAL AND ANATOMICAL CHARACTERISTICS OF STEMS OF MORUS NIGRA

    OpenAIRE

    Yu. A. Vakhrusheva; I. I. Kharchenko; A. S. Nikitina; E. T. Oganesyan

    2015-01-01

    Until now, plants have been the main source of new drugs. Morus nigra, which contains a rich complex of biologically active substances necessary for an organism (vitamins, anthocyanins, macro- and microelements, organic acids) is of great interest. We have conducted morphological and anatomical studies of stems of Morus nigra, identified the main diagnostic characters of the studied medicinal plants. Experimental studies have shown that the stems of Morus nigra are characterized by the presen...

  9. Effect of aqueous extract of Morus nigra on skin wound healing in type 1 diabetic rats

    OpenAIRE

    Mohammad Mahdi Mirjalili; Shiva Faramarzi; Manasour Esmaeilidehaj; Fatemeh Zare Mehrjardi; Mohammad Ebrahim Rezvani

    2017-01-01

    Introduction: Delay in wound healing is one of several complications of type 1 diabetes. It has been reported that the use of various herbal extracts such as Morus nigra increase the  wound healing.  Since,there are no studies on investigation of the effects of Morus nigra on wound healing in diabetics so this study was conducted to determine wound healing effects of Morus nigra in diabetic rats. Methods: In this experimental study, the fresh fruits were blended and pressed. Then...

  10. Effect of aqueous extract of Morus nigra on skin wound healing in type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohammad Mahdi Mirjalili

    2017-07-01

    Conclusion: Topical application of the Morus nigra extract can accelrate wound contraction and improve the histological indices inclue formation of epithelial and granulated layers and increase collagen density in the repaired tissue.

  11. Bioactive profile of Plakortis nigra, a sea sponge from Mauritius Islands

    OpenAIRE

    Sandrine Tangman; Joyce Govinden Soulange; Daniel Marie

    2015-01-01

    Objective: To investigate the in vitro antibacterial and antioxidant activities of crude and fractionated extracts of the Plakortis nigra (P. nigra) sea sponge from Mauritius sea waters. Methods: Preliminary qualitative chemical screening of the sponge extracts was conducted by using standard methods while the total phenolic content (TPC) was estimated through the Folin-Ciocalteu method. Antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli and Pr...

  12. Acaricidal activity of leaves of Morus nigra against the cattle tick Rhipicephalus microplus

    OpenAIRE

    Dantas, A.C.S.; Freire, D.P.; Souza, G.R.; Almeida, J.R.G.S.; Rolim, L.A.; Castro, R.N.; Horta, M.C.

    2017-01-01

    ABSTRACT The acaricidal activity of crude ethanolic extract and fractions from the leaves of Morus nigra (Moraceae) was carried out on female cattle ticks Rhipicephalus microplus, using the adult immersion test. The mortality and fertility of females exposed to different concentrations of hexane, chloroform and ethyl acetate fractions, as well as ethanolic extract of M. nigra with concentrations of 5, 10 and 25mg/ml were evaluated using three treatment groups, two control groups and triplicat...

  13. Spike-timing dependent plasticity in the striatum

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2010-06-01

    Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

  14. Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jonathan Wills

    2011-03-01

    Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

  15. Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract.

    Science.gov (United States)

    Zeni, Ana Lúcia B; Moreira, Tatianne D; Dalmagro, Ana Paula; Camargo, Anderson; Bini, Larissa A; Simionatto, Edésio L; Scharf, Dilamara R

    2017-01-01

    Morus nigra L. (Moraceae) is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN) showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively), as well as antioxidant activity (83.85%) than decoction or hydromethanolic extracts. Although, decoction showed the best result for ascorbic acid (4.35 mg/100 g) than hydromethanolic or infusion (2.51 or 2.13 mg/100 g, respectively). The phenolic acids gallic, chlorogenic and caffeic and the flavonoids quercetin, rutin and catechin were found in the M. nigra extracts. Hyperlipidemic rats treated with 100, 200 or 400 mg/kg of MN decreased serum cholesterol, triglycerides and normalized lipoproteins. Furthermore, MN inhibited lipid peroxidation in liver, kidney and brain of hyperlipidemic rats. This study provides evidence that M. nigra leaves extracts are rich in polyphenols, mainly chlorogenic acid, which normalized hyperlipidemic disturbance. The results suggest a potential therapeutic effect of the M. nigra leaves infusion on dislipidemic condition and related oxidative stress.

  16. Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract

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    ANA LÚCIA B. ZENI

    2017-12-01

    Full Text Available ABSTRACT Morus nigra L. (Moraceae is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively, as well as antioxidant activity (83.85% than decoction or hydromethanolic extracts. Although, decoction showed the best result for ascorbic acid (4.35 mg/100 g than hydromethanolic or infusion (2.51 or 2.13 mg/100 g, respectively. The phenolic acids gallic, chlorogenic and caffeic and the flavonoids quercetin, rutin and catechin were found in the M. nigra extracts. Hyperlipidemic rats treated with 100, 200 or 400 mg/kg of MN decreased serum cholesterol, triglycerides and normalized lipoproteins. Furthermore, MN inhibited lipid peroxidation in liver, kidney and brain of hyperlipidemic rats. This study provides evidence that M. nigra leaves extracts are rich in polyphenols, mainly chlorogenic acid, which normalized hyperlipidemic disturbance. The results suggest a potential therapeutic effect of the M. nigra leaves infusion on dislipidemic condition and related oxidative stress.

  17. Renal biochemical and histopathological alterations of diabetic rats under treatment with hydro alcoholic Morus nigra extrac

    Science.gov (United States)

    Rahimi-Madiseh, Mohammad; Naimi, Azar; Heydarian, Esfandiar; Rafieian-Kopaei, Mahmoud

    2017-01-01

    Introduction: Morus nigra fruit is known to have antioxidant effects and used to control the blood sugar level in traditional medicine. Objectives: This study was conducted to investigate the biochemical and histopathological changes in the serum and kidneys of diabetic rats treated with hydroalcoholic M. nigra extract. Materials and Methods: In this study, 60 male Wistar rats were divided into five groups of 12 each. After induction of diabetes with alloxan, the diabetic rats were treated with hydroalcoholic extract of M. nigra at different concentrations. Then, the animals were anesthetized and the serum levels of glucose, creatinine, and urea as well as kidney tissue catalase level measured. The kidney tissue was also histopathologically examined. Results: Milder glomerular damage was seen in the group treated with 800 mg/kg of the M. nigra extract compared with diabetic and positive controls, and no difference in the expansion of mesenchymal tissue into renal glomerular vessels observed between the group treated with 800 mg/kg of M. nigra extract and diabetic and positive controls. Furthermore, creatinine levels were significantly higher and urea levels significantly lower in the group treated with 800 mg/kg of M. nigra extract than healthy and positive control groups (Pnigra extract at 800 mg/kg can prevent kidney tissue damage in diabetic rats and this fruit seems to be beneficial to patients with diabetes. PMID:28487873

  18. Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum.

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    Kaag, Anne Marije; Schluter, Renée S; Karel, Peter; Homberg, Judith; van den Brink, Wim; Reneman, Liesbeth; van Wingen, Guido A

    2016-01-01

    Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

  19. In vitro regeneration of Salix nigra from adventitious shoots.

    Science.gov (United States)

    Lyyra, Satu; Lima, Amparo; Merkle, Scott A

    2006-07-01

    Black willow (Salix nigra Marsh.) is the largest and only commercially important willow species in North America. It is a candidate for phytoremediation of polluted soils because it is fast-growing and thrives on floodplains throughout eastern USA. Our objective was to develop a protocol for the in vitro regeneration of black willow plants that could serve as target material for gene transformation. Unexpanded inflorescence explants were excised from dormant buds collected from three source trees and cultured on woody plant medium (WPM) supplemented with one of: (1) 0.1 mg l(-1) thidiazuron (TDZ); (2) 0.5 mg l(-1) 6-benzoaminopurine (BAP); or (3) 1 mg l(-1) BAP. All plant growth regulator (PGR) treatments induced direct adventitious bud formation from the genotypes. The percentage of explants producing buds ranged from 20 to 92%, depending on genotype and treatment. Although most of the TDZ-treated inflorescences produced buds, these buds failed to elongate into shoots. Buds on explants treated with BAP elongated into shoots that were easily rooted in vitro and further established in potting mix in high humidity. The PGR treatments significantly affected shoot regeneration frequency (P < 0.01). The highest shoot regeneration frequency (36%) was achieved with Genotype 3 cultured on 0.5 mg l(-1) BAP. Mean number of shoots per explant varied from one to five. The ability of black willow inflorescences to produce adventitious shoots makes them potential targets for Agrobacterium-mediated transformation with heavy-metal-resistant genes for phytoremediation.

  20. Genetic diversity in Populus nigra plantations from west of Iran

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    Afrooz Alimohamadi

    2012-11-01

    Full Text Available In order to adopt strategies for forest conservation and development,it is necessary to estimate the amount and distribution of genetic diversity in existing populations of poplar in Iran. In this study, the genetic diversity between eight stands of Populus nigra established in Kermanshah province was evaluated on the basis of molecular and morphological markers. To amplify microsatellite loci (WPMS09, WPMS16 and WPMS18, DNA extraction from young and fresh leaveswas done. Various conditions of the PCR assay were examined and to evaluate the morphological variation of the morphological characters leaves (consist of 19 traits were measured. In addition, height growth was measured, to evaluate the growth function of the stands in homogeneous conditions. Genetic diversity in termof polymorphic loci was 0%, because three investigated microsatellite loci were monomorphic. The total number of alleles for 3 microsatellite loci was 6 (na = 2, ne = 2, heo = 1, hee = 0.51. Genetic identity based on Nei was 100%, so genetic distance was 0%. The whole sampled trees represented the same thus the genotype. No significant differences between the mean values of all morphological characters and height growth were revealed. Observed genetic similarity gave indication that same ramets had been selected to plant in poplar plantation established in Kermanshah province.These results suggest the need for an initial evaluation of the genetic diversity in selected ramets for planting in plantation to avoid repetition.

  1. Antiplasmodial Alkaloids from the Bark of Cryptocarya nigra (Lauraceae

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    Khalijah Awang

    2013-07-01

    Full Text Available A dichloromethane extract of the stem bark of Cryptocarya nigra showed strong in vitro inhibition of Plasmodium falciparum growth, with an IC50 value of 2.82 μg/mL. The phytochemical study of this extract has led to the isolation and characterization of four known alkaloids: (+-N-methylisococlaurine (1, atherosperminine (2, 2-hydroxyathersperminine (3, and noratherosperminine (4. Structural elucidation of all alkaloids was accomplished by means of high field 1D- and 2D-NMR, IR, UV and LCMS spectral data. The isolated extract constituents (+-N-methylisococlaurine (1, atherosperminine (2 and 2-hydroxy-atherosperminine (3 showed strong antiplasmodial activity, with IC50 values of 5.40, 5.80 and 0.75 μM, respectively. In addition, (+-N-methylisocolaurine (1 and atherosperminine (2 showed high antioxidant activity in a DPPH assay with IC50 values of 29.56 ug/mL and 54.53 ug/mL respectively. Compounds 1 and 2 also both showed high antioxidant activity in the FRAP assay, with percentages of 78.54 and 70.66 respectively and in the metal chelating assay, with IC50 values of 50.08 ug/mL and 42.87 ug/mL, respectively.

  2. Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL-VBM study.

    Science.gov (United States)

    Colloby, Sean J; Elder, Greg J; Rabee, Riham; O'Brien, John T; Taylor, John-Paul

    2017-06-01

    Several cholinergic nuclei, and in particular the nucleus basalis of Meynert, are localised to the substantia innominata in the basal forebrain. These nuclei provide major cholinergic innervation to the cerebral cortex and hippocampus, and have an essential role in cognitive function. The aim of this study was to investigate volumetric grey matter (GM) changes in the substantia innominata from structural T1 images in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy older participants using voxel-based morphometry. Participants (41 DLB, 47 AD and 39 controls) underwent 3 T T1 magnetic resonance imaging and cognitive assessments. Voxel-based morphometry analysis used SPM8 with a substantia innominata brain mask to define the subspace for voxel GM analyses. Group differences, and selected behavioural and clinical correlates, were assessed. Compared with that in controls, bilateral GM loss in the substantia innominata was apparent in both AD and DLB. Relative to controls, significant bilateral GM loss in the substantia innominata was observed in DLB and AD. In DLB, significant associations were also observed between substantia innominata GM volume loss, and the levels of cognitive impairment and severity of cognitive fluctuations. Relative to that controls, atrophy of the substantia innominata was apparent in DLB and AD, and is associated with specific clinical manifestations in DLB. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

  3. Molluscicidal activity of Morus nigra against the freshwater snail Lymnaea acuminata

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    Farheen Hanif

    2012-01-01

    Full Text Available The molluscicidal activity of Morus nigra fruit, bark and leaf powder against the snail Lymnaea acuminata was time and concentration dependent. Toxicity of fruit powder (96h LC50: 166.92 mg/L was more pronounced in comparison to bark powder (96h LC50: 173.17 mg/L and leaf powder (96h LC50: 173.69 mg/L. Ethanolic extracts of M. nigra fruit, bark and leaf was more toxic than their other organic solvent extracts. The molluscicidal activity of ethanolic extract of M. nigra fruit powder (24h LC50: 116.23 mg/L was more effective than the ethanolic extract of bark powder (24h LC50: 154.41 mg/L and leaf powder (24h LC50: 139.80 mg/L. The 96h LC50 of column-purified fraction of M. nigra fruit powder was, 10.03 mg/L whereas that of bark and leaf powder was 8.69 mg/L and 4.97 mg/L, respectively. Column and thin layer chromatography analysis demonstrates that the active molluscicidal component in M. nigra is quercetin (96h LC50: 1.11 mg/L, apigenin (96h LC50: 1.92 mg/L and morusin (96h LC50: 2.12 mg/L, respectively. Co-migration of quercetin (Rf 0.49, apigenin (Rf 0.51 and morusin (Rf 0.52 with column-purified fruit, bark and leaf of M. nigra on thin layer chromatography demonstrates same Rf value. The present study indicates that M. nigra may be used as potent source of molluscicides against the snail Lymnaea acuminata.

  4. The proteome of Populus nigra woody root: response to bending

    Science.gov (United States)

    Trupiano, Dalila; Rocco, Mariapina; Renzone, Giovanni; Scaloni, Andrea; Viscosi, Vincenzo; Chiatante, Donato; Scippa, Gabriella S.

    2012-01-01

    Background and Aims Morphological and biomechanical alterations occurring in woody roots of many plant species in response to mechanical stresses are well documented; however, little is known about the molecular mechanisms regulating these important alterations. The first forest tree genome to be decoded is that of Populus, thereby providing a tool with which to investigate the mechanisms controlling adaptation of woody roots to changing environments. The aim of this study was to use a proteomic approach to investigate the response of Populus nigra woody taproot to mechanical stress. Methods To simulate mechanical perturbations, the taproots of 30 one-year-old seedlings were bent to an angle of 90 ° using a steel net. A spatial and temporal two-dimensional proteome map of the taproot axis was obtained. We compared the events occurring in the above-bending, central bending and below-bending sectors of the taproot. Key Results The first poplar woody taproot proteome map is reported here; a total of 207 proteins were identified. Spatial and temporal proteomic analysis revealed that factors involved in plant defence, metabolism, reaction wood formation and lateral root development were differentially expressed in the various sectors of bent vs. control roots, seemingly in relation to the distribution of mechanical forces along the stressed woody taproots. A complex interplay among different signal transduction pathways involving reactive oxygen species appears to modulate these responses. Conclusions Poplar woody root uses different temporal and spatial mechanisms to respond to mechanical stress. Long-term bending treatment seem to reinforce the defence machinery, thereby enabling the taproot to better overcome winter and to be ready to resume growth earlier than controls. PMID:22437664

  5. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...

  6. Mycorrhization of containerised Pinus nigra seedlings with Suillus granulatus under open field conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lazarevic, J.; Keca, N.; Martinovie, A.

    2012-07-01

    Seedling mycorrhization acts as an efficient tool for improving the quality of seedlings. In this study, the effectiveness of Suillus granulatus, originating from Pinus heldreichii forests (Montenegro), to produce containerized ectomycorrhizal seedlings of autochthonous Pinus nigra in open field conditions was investigated. Spore (106, 107, 108) and vegetative (1:16, 1:8, 1:4) inoculation on ectomycorrhizal formation and seedling growth were tested. Spore and vegetative inoculums of autochthonous Pisolithus arhizus were used in the same trial as additional control treatments. The utilization of vegetative and spore inoculums of autochthonous S. granulatus has proven to be an effective method of obtaining containerized ectomycorrhizal P. nigra seedlings under open field conditions after 11 months. S. granulatus spore inoculations resulted in well developed ectomycorrhiza, decreasing the growth of the P. nigra seedlings in the first growing season. Mycelial inoculations resulted in slightly developed S. granulatus ectomycorrhiza, which increased the growth of the seedlings. Therefore, it would be feasible to use spore inocula of S. granulatus, with 10{sup 6} spores per plant, to produce ectomycorrhizal P. nigra plants on a large scale. Controlled mycorrhizal inoculation of seedlings is not a common practice in Montenegrin and Serbian nurseries; as such, the obtained results will contribute to the enhancement of nursery production of Pinus nigra and other conifers. This also could be assumed as a starting point for many further efforts and investigations with autochthonous fungal and plant material in this region. (Author) 47 refs.

  7. The nigrostriatal pathway: axonal collateralization and compartmental specificity.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A; Bernácer, J; Cebrián, C

    2009-01-01

    This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

  8. Chemical architecture of the posterior striatum in the human brain.

    Science.gov (United States)

    Bernácer, J; Prensa, L; Giménez-Amaya, J M

    2008-01-01

    The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum.

  9. THE STUDY OF MORPHOLOGICAL AND ANATOMICAL CHARACTERISTICS OF STEMS OF MORUS NIGRA

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    Yu. A. Vakhrusheva

    2015-01-01

    Full Text Available Until now, plants have been the main source of new drugs. Morus nigra, which contains a rich complex of biologically active substances necessary for an organism (vitamins, anthocyanins, macro- and microelements, organic acids is of great interest. We have conducted morphological and anatomical studies of stems of Morus nigra, identified the main diagnostic characters of the studied medicinal plants. Experimental studies have shown that the stems of Morus nigra are characterized by the presence of thick-walled epidermal cells with slightly convoluted walls and a large number of ordinary thick-walled fuzz.

  10. Insights into some physiological and biochemical responses of Populus alba and Populus nigra to lead contamination

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    Elham Etemadi

    2016-12-01

    Full Text Available The effects of lead (PbCl2 increment, under hydroponic conditions up to 15, 45 and 90 mg/l in presence of EDTA, on some physiological and biochemical traits of one year old saplings of P. nigra and P. alba, were investigated. Six weeks after establishing in target concentration, the amount of lead, biomass, water, soluble sugars, proline, electrolyte leakage, malondialdehyde, and pigments were assessed in different organs. The results revealed that with increasing lead concentration in culture medium in the studied period, the amount of lead in saplings increased, but no effect was observed on their biomass. In both species the magnitude of lead accumulation in root was higher than leaf. P. nigra had more water and less soluble sugars than P. alba. The concentration of soluble sugars increased up to 1.5 times with lead increment in both species, but proline content increased only in P. nigra up to 2 times and remained constant in P. alba. Elevation of electrolyte leakage in saplings of P. nigra in excess lead treatment was accompanied by no change in malondialdehyde content. Concentrations of pigments were not affected by lead, and only the ratio of chlorophyll a to b in P. nigra increased in high lead concentration. In general both species accumulated high extent of lead in their organs. But it seems that P. nigra, at least with respect of enhancing plasma membrane permeability, increasing proline and the ratio of chlorophyll a to b, was more sensitive to this toxic metal in compare with P. alba.

  11. Development of Brassica oleracea-nigra monosomic alien addition lines: genotypic, cytological and morphological analyses.

    Science.gov (United States)

    Tan, Chen; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

    2017-12-01

    We report the development and characterization of Brassica oleracea - nigra monosomic alien addition lines (MAALs) to dissect the Brassica B genome. Brassica nigra (2n = 16, BB) represents the diploid Brassica B genome which carries many useful genes and traits for breeding but received limited studies. To dissect the B genome from B. nigra, the triploid F 1 hybrid (2n = 26, CCB) obtained previously from the cross B. oleracea var. alboglabra (2n = 18, CC) × B. nigra was used as the maternal parent and backcrossed successively to parental B. oleracea. The progenies in BC 1 to BC 3 generations were analyzed by the methods of FISH and SSR markers to screen the monosomic alien addition lines (MAALs) with each of eight different B-genome chromosomes added to C genome (2n = 19, CC + 1B 1-8 ), and seven different MAALs were established, except for the one with chromosome B2 which existed in one triple addition. Most of these MAALs were distinguishable morphologically from each other, as they expressed the characters from B. nigra differently and at variable extents. The alien chromosome remained unpaired as a univalent in 86.24% pollen mother cells at diakinesis or metaphase I, and formed a trivalent with two C-genome chromosomes in 13.76% cells. Transmission frequency of all the added chromosomes was far higher through the ovules (averagely 14.40%) than the pollen (2.64%). The B1, B4 and B5 chromosomes were transmitted by female at much higher rates (22.38-30.00%) than the other four (B3, B6, B7, B8) (5.04-8.42%). The MAALs should be valuable for exploiting the genome structure and evolution of B. nigra.

  12. An NR2B-Dependent Decrease in the Expression of trkB Receptors Precedes the Disappearance of Dopaminergic Cells in Substantia Nigra in a Rat Model of Presymptomatic Parkinson's Disease

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    Eduardo Riquelme

    2012-01-01

    Full Text Available Compensatory changes occurring during presymptomatic stages of Parkinson's disease (PD would explain that the clinical symptoms of the disease appear late, when the degenerative process is quite advanced. Several data support the proposition that brain-derived neurotrophic factor (BDNF could play a role in these plastic changes. In the present study, we evaluated the expression of the specific BDNF receptor, trkB, in a rat model of presymptomatic PD generated by intrastriatal injection of the neurotoxin 6-OHDA. Immunohistochemical studies revealed a decrease in trkB expression in SN pars compacta (SNc seven days after 6-OHDA injection. At this time point, no change in the number of tyrosine hydroxylase (TH immunoreactive (TH-IR cells is detected, although a decrease is evident 14 days after neurotoxin injection. The decrease in TH-positive cells and trkB expression in SNc was significantly prevented by systemic administration of Ifenprodil, a specific antagonist of NR2B-containing NMDA receptors. Therefore, an NR2B-NMDA receptor-dependent decrease in trkB expression precedes the disappearance of TH-IR cells in SNc in response to 6-OHDA injection. These results support the idea that a functional coupling between NMDA receptors and BDNF/trkB signalling may be important for the maintenance of the dopaminergic phenotype in SNc during presymptomatic stages of PD.

  13. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons.

    Science.gov (United States)

    Huang, Chung-Yu; Chen, Ying-Ling; Li, Allen H; Lu, Juu-Chin; Wang, Hung-Li

    2014-01-10

    Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia. Following intrathecal co

  14. Gambling and the need for new responses in Public Health with an addiction "sine substantia".

    Science.gov (United States)

    Crusco, M; Massoni, F; Luzi, E; Ricci, P; Pelosi, M; Corbosiero, P; Rapp-Ricciardi, M; Ricci, S

    2016-01-01

    The Gambling Disorder (GD) was recently defined as a behavioral addiction by the "The Diagnostic and Statistical Manual of Mental Disorders IV"( DSM-V) since the clinical, neurobiological and psychopathological similarities led it to be defined it as an addiction "sine substantia". The aim of this study is to formulate an "identikit" of the gambler, to evaluate a possible association between GD / emotional specific factors and the correlation between GD / substance abuse, GD / suicide. In the study, 41 subjects were included (31 males and 10 females) and all were diagnosed with GD. A questionnaire was distributed containing 24 questions deriving from South Oaks Gambling Screen and the DSM-IVTR. The study showed that 51% of the respondents makes use of alcohol and / or drugs; that 73% of the patients started playing in order to relieve feelings of dysphoria and suffering consequences on work as well as family life (51%). A great deal of the respondents were indebted (39%) to the extent of needing to ask for loans from usurer (17%). Furthermore, 41% of the respondents in the sample showed that GD could be transformed into an alarming risk of suicide. The correlation between GD and drug abuse may depend on the brain function and the neural circuits that support impulsive behavior and the gratification mechanisms. Emotional experiences (stress, low level of education, divorce, poor social support) could constitute a possible risk factor that increases the GD. The committed offenses related to gambling could be explained by "loss of control". The results of the present study contributes to the body of knowledge regarding the size of phenomenon from a statistical and epidemiological point of view, suggesting the necessity for targeted information on the risks connected to GD in order to capture early warning signs which enables the intervention with suitable strategies.

  15. Kinetic diversity of dopamine transmission in the dorsal striatum.

    Science.gov (United States)

    Taylor, I Mitch; Nesbitt, Kathryn M; Walters, Seth H; Varner, Erika L; Shu, Zhan; Bartlow, Kathleen M; Jaquins-Gerstl, Andrea S; Michael, Adrian C

    2015-05-01

    Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat. Thus, it becomes necessary to consider how these domains might be related to specific aspects of DA's functions. Responses evoked in the fast and slow domains are distinct in both amplitude and temporal profile. Herein, we report that responses evoked in fast domains can be further classified into four distinct types, types 1-4. The DS, therefore, exhibits a total of at least five distinct evoked responses (four fast types and one slow type). All five response types conform to kinetic models based entirely on first-order rate expressions, which indicates that the heterogeneity among the response types arises from kinetic diversity within the DS terminal field. We report also that functionally distinct subregions of the DS express DA kinetic diversity in a selective manner. Thus, this study documents five response types, provides a thorough kinetic explanation for each of them, and confirms their differential association with functionally distinct subregions of this key DA terminal field. The dorsal striatum is composed of five significantly different dopamine domains (types 1-4 and slow, average ± SEM responses to medial forebrain bundle (MFB) stimulation are shown in the figure). Responses from each of these five domains exhibit significantly different ascending and descending kinetic profiles and return to a long lasting elevated dopamine state, termed the dopamine hang-up. All features of these responses are modeled with high correlation using first-order modeling as well as our recently published restricted diffusion

  16. Language Processing within the Striatum: Evidence from a PET Correlation Study in Huntington's Disease

    Science.gov (United States)

    Teichmann, Marc; Gaura, Veronique; Demonet, Jean-Francois; Supiot, Frederic; Delliaux, Marie; Verny, Christophe; Renou, Pierre; Remy, Philippe; Bachoud-Levi, Anne-Catherine

    2008-01-01

    The role of sub-cortical structures in language processing, and more specifically of the striatum, remains controversial. In line with psycholinguistic models stating that language processing implies both the recovery of lexical information and the application of combinatorial rules, the striatum has been claimed to be involved either in the…

  17. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  18. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M.; Groblewski, Peter A.; Phillips, Paul E. M.

    2014-01-01

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  19. Art for reward's sake: visual art recruits the ventral striatum.

    Science.gov (United States)

    Lacey, Simon; Hagtvedt, Henrik; Patrick, Vanessa M; Anderson, Amy; Stilla, Randall; Deshpande, Gopikrishna; Hu, Xiaoping; Sato, João R; Reddy, Srinivas; Sathian, K

    2011-03-01

    A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non-art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Response inhibition signals and miscoding of direction in dorsomedial striatum

    Directory of Open Access Journals (Sweden)

    Daniel W Bryden

    2012-09-01

    Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

  1. Chemical heterogeneity of the striosomal compartment in the human striatum.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A

    1999-11-01

    The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture. Copyright 1999 Wiley-Liss, Inc.

  2. Effect of variety on content of bioactive phenolic compounds in common elder (Sambucus nigra L.)

    Czech Academy of Sciences Publication Activity Database

    Vrchotová, Naděžda; Dadáková, E.; Matějíček, A.; Tříska, Jan; Kaplan, J.

    2017-01-01

    Roč. 31, č. 6 (2017), s. 700-703 ISSN 1478-6419 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : Sambucus nigra * flavonoids * phenolic acids * HPLC-MS Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 1.828, year: 2016

  3. Wood Anatomical Structure of Morus alba L. and Morus nigra L., Native to Iran

    Directory of Open Access Journals (Sweden)

    Elham KARAMI

    2010-12-01

    Full Text Available Iran is a wast country with many different tree species. Among those there are two species of Morus genus including alba and nigra. Since long time ago, white mulberry�s wood (Morus alba has been used for making musical instruments especially bowl shaped instruments in Iran.. In contrast, black mulberry�s wood (Morus nigra has never been used for these types of applications. In order to investigate the possible replacement choices, this study has been carried out to investigate the anatomical differences and similarities between these two species. Wood samples of the two species have been collected from same site and microsections for light microscopic studies and maceration samples have been prepared. The anatomical characteristics were studied according to the IAWA List of Hardwoods. The most important similarities between them are: vessel solitary in short radial multiples or irregular clusters, fiber nonseptate, rays uniseriate and multiseriate type, paratracheal parenchyma, varying from vasicentric to aliform confluent, apotracheal as marginal bands, Rhombic crystals present in rays and sometimes in parenchyma. The main differences are: semi-ring porous distribution of vessels in M. alba, fewer number of vessels and presence of aliform parenchyma in M. nigra. Taking these results into consideration, the most important features of both species are similar and it could be recommended to use the nigra species as well as the alba for making musical instruments.

  4. Developing new microsatellite markers in walnut (Juglans regia L.) from Juglans nigra genomic GA enriched library

    Science.gov (United States)

    Hayat Topcu; Nergiz Coban; Keith Woeste; Mehmet Sutyemez; Salih. Kafkas

    2015-01-01

    We attempted to develop new polymorphic SSR primer pairs in walnut using sequences derived from Juglans nigra L. genomic enriched library with GA repeat. The designed 94 SSR primer pairs were subjected to gradient PCR in 12 walnut cultivars to determine their optimum annealing temperatures and to determine whether they produce bands. Then, the...

  5. Ozone affects growth and development of Pieris brassicae on the wild host plant Brassica nigra

    NARCIS (Netherlands)

    Khaling, E.; Papazian, S.; Poelman, E.H.; Holopainen, J.K.; Albrectsen, B.R.; Blande, J.D.

    2015-01-01

    When plants are exposed to ozone they exhibit changes in both primary and secondary metabolism, which may affect their interactions with herbivorous insects. Here we investigated the performance and preferences of the specialist herbivore Pieris brassicae on the wild plant Brassica nigra under

  6. First Record of Dicheilonema Ciconiae (Nematoda, Diplotriaenoidea From Ciconia Nigra (Aves, Ciconiidae in Ukraine

    Directory of Open Access Journals (Sweden)

    Syrota Ya. Yu.

    2016-08-01

    Full Text Available Five specimens of a parasitic nematode Dicheilonema ciconiae (Schrank, 1788 were collected from black stork, Ciconia nigra Linnaeus, in Kyiv Zoological Park. Identification of the nematodes was confirmed by morphological examination of the specimens collected. The ornamentation of the body cuticle in caudal region of males (area rugosa is first described in D. ciconiae.

  7. Habitat characteristics at den sites of the Point Arena mountain beaver (Aplodontia rufa nigra)

    Science.gov (United States)

    William J. Zielinski; John E. Hunter; Robin Hamlin; Keith M. Slauson; M. J. Mazurek

    2010-01-01

    The Point Arena mountain beaver (Aplodontia rufa nigra) is a federally listed endangered species, but has been the subject of few studies. Mountain beavers use burrows that include a single subterranean den. Foremost among the information needs for this subspecies is a description of the above-ground habitat features associated with dens. Using...

  8. Reproductive characteristics of the Point Arena mountain beaver (Aplodontia rufa nigra)

    Science.gov (United States)

    William Zielinski; M. J. Mazurek

    2016-01-01

    Little is known about the ecology and life history of the federally endangered Point Arena mountain beaver (Aplodontia rufa nigra). The distribution of this primitive burrowing rodent is disjunct from the balance of the species’ range and occurs in a unique maritime environment of coastal grasslands and forests. Fundamental to protecting this taxon...

  9. Development and characterization of microsatellite markers in the Point Arena mountain beaver Aplodontia rufa nigra

    Science.gov (United States)

    Kristine L. Pilgrim; William J. Zielinski; Mary J. Mazurek; Frederick V. Schlexer; Michael K. Schwartz

    2006-01-01

    The Point Arena mountain beaver (Aplodontia rufa nigra) is an endangered subspecies. Efforts to recover this sub-species will be aided by advances in molecular genetics, specifically the ability to estimate population size using noninvasive genetic sampling. Here we report on the development of nine polymorphic loci for the Point Arena mountain...

  10. Cultivar identification and genetic relatedness among 25 black walnut (Juglans nigra) clones based on microsatellite markers

    Science.gov (United States)

    Kejia Pang; Keith Woeste; Charles. Michler

    2017-01-01

    A set of eight microsatellite markers was used to genotype 25 black walnut (Juglans nigra L.) clones within the Purdue University germplasm repository. The identities of 212 ramets were verified using the same eight microsatellite markers. Some trees were mislabeled and corrected as to clone using analysis of microsatellite markers. A genetic...

  11. Assessment of Black Ash (Fraxinus nigra) Decline in Minnesota. Chapter 12

    Science.gov (United States)

    Brian J. Palik; Michael E. Ostry; Robert C. Venette; Kathleen T. Ward

    2012-01-01

    Black ash (Fraxinus nigra) is present throughout the upper Midwest and Northeastern United States and is often found in lowland hardwood forests. Black ash seed is an important food for birds and small mammals, and its twigs and foliage are used by ungulates. Black ash wood is valued for paneling and furniture as well as for Native American basketry...

  12. ANTIOXIDANT ACTIVITY OF TISSUE CULTURE-RAISED BALLOTA NIGRA L. PLANTS GROWN EX VITRO.

    Science.gov (United States)

    Makowczyńska, Joanna; Grzegorczyk-KAROLAK, Izabela; Wysokińska, Halina

    2015-01-01

    Antioxidant properties and total phenolic and flavonoid contents were evaluated in methanolic extracts of shoots from Ballota nigra plants initiated in vitro (from nodal explants) and in vivo (from seeds). The plants were grown in greenhouse and in the field, and were analyzed at the vegetative and flowering stages. The shoot extract of wild-grown plants of B. nigra was also investigated. The results indicate that antioxidant potential of the B. nigra extracts seems to be due to their scavenging of free radicals (DPPH assay) and metal reducing (FRAP test), while they were less effective at the prevention of linoleic acid peroxidation (LPO test). The extracts from shoots of in vitro derived plants were found to exhibit the greatest antioxidant properties. The extracts were also characterized by the highest content of phenolic compounds and their level was affected by plant developmental stage. The extracts of shoots collected at the flowering period exhibited higher amounts of phenolics and flavonoids than in the extracts of immature plants. A close correlation between the total phenolic content and flavonoid content and antioxidant activity using the DPPH and FRAP assays was obtained. The results of the present study suggest the use in vitro-derived plants of B. nigra instead of using wild plants for pharmaceutical purposes.

  13. Inhibiting PKM[zeta] Reveals Dorsal Lateral and Dorsal Medial Striatum Store the Different Memories Needed to Support Adaptive Behavior

    Science.gov (United States)

    Pauli, Wolfgang M.; Clark, Alexandra D.; Guenther, Heidi J.; O'Reilly, Randall C.; Rudy, Jerry W.

    2012-01-01

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or…

  14. Complete mitochondrial genome sequence of black mustard (Brassica nigra; BB) and comparison with Brassica oleracea (CC) and Brassica carinata (BBCC).

    Science.gov (United States)

    Yamagishi, Hiroshi; Tanaka, Yoshiyuki; Terachi, Toru

    2014-11-01

    Crop species of Brassica (Brassicaceae) consist of three monogenomic species and three amphidiploid species resulting from interspecific hybridizations among them. Until now, mitochondrial genome sequences were available for only five of these species. We sequenced the mitochondrial genome of the sixth species, Brassica nigra (nuclear genome constitution BB), and compared it with those of Brassica oleracea (CC) and Brassica carinata (BBCC). The genome was assembled into a 232 145 bp circular sequence that is slightly larger than that of B. oleracea (219 952 bp). The genome of B. nigra contained 33 protein-coding genes, 3 rRNA genes, and 17 tRNA genes. The cox2-2 gene present in B. oleracea was absent in B. nigra. Although the nucleotide sequences of 52 genes were identical between B. nigra and B. carinata, the second exon of rps3 showed differences including an insertion/deletion (indel) and nucleotide substitutions. A PCR test to detect the indel revealed intraspecific variation in rps3, and in one line of B. nigra it amplified a DNA fragment of the size expected for B. carinata. In addition, the B. carinata lines tested here produced DNA fragments of the size expected for B. nigra. The results indicate that at least two mitotypes of B. nigra were present in the maternal parents of B. carinata.

  15. Alleviation of overtraining reversal effect by transient inactivation of the dorsal striatum.

    Science.gov (United States)

    Van Golf Racht-Delatour, B; Massioui, N E

    2000-09-01

    In this study, we investigated the role of the dorsal striatum in the acquisition and the use (retrieval) of a specific learning developed during overtraining. The paradigm was such that rats had to respond differentially to two signals in order to obtain food or to avoid an electrical footshock. Overtraining was aimed at eliciting a facilitative effect on discrimination reversal as compared to simply trained rats. In this way, transient inactivation of the dorsal striatum by lidocaine enabled us to investigate, separately, the role of this structure during overtraining and reversal. The data show that inactivating the dorsal striatum before each reversal session prevented the overtraining reversal effect observed in control rats. Moreover, inactivation of the dorsal striatum during overtraining had no effect on the level of discriminative performance just as it did not affect the subsequent facilitative effect on reversal. These results show that even though the striatum might normally be part of a routine automatic system, clearly its contribution is not essential. Indeed, despite inactivation of the striatum in overtrained rats, their ability to develop an efficient selection process that can be used during reversal was observed. However, the integrity of the striatum became essential in order to mediate the modification of behaviour when this behavioural routine formed during overtraining had to be modified during reversal.

  16. 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.

  17. The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

    Science.gov (United States)

    Cole, Sindy; Stone, Andrew D; Petrovich, Gorica D

    2017-12-01

    The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning. Rats with DMS lesions selectively attenuated responding to a food cue but not a control cue, early in training, suggesting the DMS is involved when initial associations are formed. Similarly, initial reversal learning was attenuated in rats with DMS lesions, which suggests impaired flexibility to adjust behavior when the cue meaning is reversed. We also examined the effect of DMS lesions on food intake during tests with access to a highly palatable food along with standard chow diet. Rats with DMS lesions showed an altered pattern of intake, with an initial reduction in high-fat diet followed by an increase in chow consumption. These results demonstrate that the DMS has a role in mediating cue-food learning and its subsequent reversal, as well as changes in food intake when a choice is provided. Together, these results demonstrate the DMS is involved in reward associative learning and reward consumption, when behavioral flexibility is needed to adjust responding or consumption to match the current value. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

    Directory of Open Access Journals (Sweden)

    Todd M. Mowery

    2017-06-01

    Full Text Available Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL, are commonly linked with processing deficits at or below the level of the auditory cortex (ACx. However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.

  19. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

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    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  20. Genetic differentiation and spatial structure of Geosmithia morbida, the causal agent of thousand cankers disease in black walnut (Juglans nigra)

    Czech Academy of Sciences Publication Activity Database

    Hadziabdic, D.; Vito, L.; Windham, M. T.; Pscheidt, J. W.; Trigiano, R. N.; Kolařík, Miroslav

    2014-01-01

    Roč. 60, č. 2 (2014), s. 75-87 ISSN 0172-8083 Institutional support: RVO:61388971 Keywords : Thousand cankers disease * Juglans nigra * Geosmithia morbida Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.682, year: 2014

  1. A New Record of Chaunocephalus ferox (Digenea, Echinostomatidae from Ciconia nigra in Ukraine Including Morphological and Molecular Data

    Directory of Open Access Journals (Sweden)

    Greben О. B.

    2016-04-01

    Full Text Available Morphological and molecular data on the type-species of Chaunocephalus Dietz, 1910, Chaunocephalus ferox (Rudolphi, 1795 is provided based on material collected from the type-host, Ciconia nigra (Linnaeus, from Kiev Zoo, Ukraine.

  2. Dissociated sequential activity and stimulus encoding in the dorsomedial striatum during spatial working memory.

    Science.gov (United States)

    Akhlaghpour, Hessameddin; Wiskerke, Joost; Choi, Jung Yoon; Taliaferro, Joshua P; Au, Jennifer; Witten, Ilana B

    2016-09-16

    Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1-4 s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10 s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum to spatial working memory.

  3. Task-specific contribution of the human striatum to perceptual-motor skill learning.

    Science.gov (United States)

    Cavaco, Sara; Anderson, Steven W; Correia, Manuel; Magalhaes, Marina; Pereira, Claudia; Tuna, Assuncao; Taipa, Ricardo; Pinto, Pedro; Pinto, Claudia; Cruz, Romeu; Lima, Antonio Bastos; Castro-Caldas, Alexandre; da Silva, Antonio Martins; Damasio, Hanna

    2011-01-01

    Acquisition of new perceptual-motor skills depends on multiple brain areas, including the striatum. However, the specific contribution of each structure to this type of learning is still poorly understood. Focusing on the striatum, we proposed (a) to replicate the finding of impaired rotary pursuit (RP) and preserved mirror tracing (MT) in Huntington's disease (HD); and (b) to further explore this putative learning dissociation with other human models of striatal dysfunction (i.e., Parkinson's disease and focal vascular damage) and two new paradigms (i.e., Geometric Figures, GF, and Control Stick, CS) of skill learning. Regardless of the etiology, participants with damage to the striatum showed impaired learning of visuomotor tracking skills (i.e., RP and GF), whereas the ability to learn skills that require motor adaptation (i.e., MT and CS) was not affected. These results suggest a task-specific involvement of the striatum in the early stages of skill learning.

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

    Science.gov (United States)

    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.

  5. Dopaminergic modulation of the functional ventrodorsal architecture of the human striatum

    NARCIS (Netherlands)

    Piray, P.; Ouden, H.E.M. den; Schaaf, M.E. van der; Toni, I.; Cools, R.

    2017-01-01

    Interactions between motivational, cognitive, and motor regions of the striatum are crucial for implementing behavioral control. Work with experimental animals indicates that such interactions are sensitive to modulation by dopamine. Using systematic pharmacological manipulation of dopamine

  6. Reproductive biology and food habits of Pseudoboa nigra (Serpentes: Dipsadidae from the Brazilian cerrado

    Directory of Open Access Journals (Sweden)

    Renata de Paula Orofino

    2010-07-01

    Full Text Available Herein we provide data on body size, sexual size dimorphism,reproductive cycle, and food habits of the pseudoboini snake Pseudoboa nigra, which is distributed mainly in central South America throughout the Cerrado domain. Based on dissections of 147 preserved specimens, it is shown that females attain, and mature at,larger body sizes than males. There is no significant sexual dimorphism in head length, but males have longer tails relative to their body sizes. Vitellogenesis, egg-laying, and sperm production occur throughout the year, but males do not exhibit long-term sperm storage. The main prey of P. nigra is lizards; there is no evidence of ontogenetic change or sex differences in the diet of this species.

  7. Green synthesis of silver nanoparticles from seed extract of Brassica nigra and its antibacterial activity

    Directory of Open Access Journals (Sweden)

    RAKSHA PANDIT

    2015-05-01

    Full Text Available Pandit R. 2015. Green synthesis of silver nanoparticles from seed extract of Brassica nigra and its antibacterial activity. Nusantara Bioscience 7: 15-19. We report the green synthesis of silver nanoparticles using seed extract of Brassica nigra. UV-visible spectroscopic analysis showed the absorbance peak at 432 nm which indicated the synthesis of silver nanoparticles. Nanoparticles Tracking and Analysis (NTA was used to determine the size of synthesized silver nanoparticles. Zeta potential analysis was carried out to study the stability of nanoparticles while FTIR analysis confirmed the presence of proteins as capping agents that provided stability to nanoparticles in colloid. Antibacterial activity of silver nanoparticles was evaluated against Propionibacterium acnes, Pseudomonas aeruginosa and Klebsiella pneumoniae. The activity of Vancomycin was significantly increased in combination with silver nanoparticles showing synergistic activity against all bacteria while the maximum activity was noted against P. acnes.

  8. The Interaction between Root Herbivory and Competitive Ability of Native and Invasive-Range Populations of Brassica nigra.

    Directory of Open Access Journals (Sweden)

    Ayub M O Oduor

    Full Text Available The evolution of increased competitive ability (EICA hypothesis predicts that escape from intense herbivore damage may enable invasive plants to evolve higher competitive ability in the invasive range. Below-ground root herbivory can have a strong impact on plant performance, and invasive plants often compete with multiple species simultaneously, but experimental approaches in which EICA predictions are tested with root herbivores and in a community setting are rare. Here, we used Brassica nigra plants from eight invasive- and seven native-range populations to test whether the invasive-range plants have evolved increased competitive ability when competing with Achillea millefolium and with a community (both with and without A. millefolium. Further, we tested whether competitive interactions depend on root herbivory on B. nigra by the specialist Delia radicum. Without the community, competition with A. millefolium reduced biomass of invasive- but not of native-range B. nigra. With the community, invasive-range B. nigra suffered less than native-range B. nigra. Although the overall effect of root herbivory was not significant, it reduced the negative effect of the presence of the community. The community produced significantly less biomass when competing with B. nigra, irrespective of the range of origin, and independent of the presence of A. millefolium. Taken together, these results offer no clear support for the EICA hypothesis. While native-range B. nigra plants appear to be better in dealing with a single competitor, the invasive-range plants appear to be better in dealing with a more realistic multi-species community. Possibly, this ability of tolerating multiple competitors simultaneously has contributed to the invasion success of B. nigra in North America.

  9. The Interaction between Root Herbivory and Competitive Ability of Native and Invasive-Range Populations of Brassica nigra

    Science.gov (United States)

    Oduor, Ayub M. O.; Stift, Marc; van Kleunen, Mark

    2015-01-01

    The evolution of increased competitive ability (EICA) hypothesis predicts that escape from intense herbivore damage may enable invasive plants to evolve higher competitive ability in the invasive range. Below-ground root herbivory can have a strong impact on plant performance, and invasive plants often compete with multiple species simultaneously, but experimental approaches in which EICA predictions are tested with root herbivores and in a community setting are rare. Here, we used Brassica nigra plants from eight invasive- and seven native-range populations to test whether the invasive-range plants have evolved increased competitive ability when competing with Achillea millefolium and with a community (both with and without A. millefolium). Further, we tested whether competitive interactions depend on root herbivory on B. nigra by the specialist Delia radicum. Without the community, competition with A. millefolium reduced biomass of invasive- but not of native-range B. nigra. With the community, invasive-range B. nigra suffered less than native-range B. nigra. Although the overall effect of root herbivory was not significant, it reduced the negative effect of the presence of the community. The community produced significantly less biomass when competing with B. nigra, irrespective of the range of origin, and independent of the presence of A. millefolium. Taken together, these results offer no clear support for the EICA hypothesis. While native-range B. nigra plants appear to be better in dealing with a single competitor, the invasive-range plants appear to be better in dealing with a more realistic multi-species community. Possibly, this ability of tolerating multiple competitors simultaneously has contributed to the invasion success of B. nigra in North America. PMID:26517125

  10. Bioactive profile of Plakortis nigra, a sea sponge from Mauritius Islands

    Directory of Open Access Journals (Sweden)

    Sandrine Tangman

    2015-01-01

    Full Text Available Objective: To investigate the in vitro antibacterial and antioxidant activities of crude and fractionated extracts of the Plakortis nigra (P. nigra sea sponge from Mauritius sea waters. Methods: Preliminary qualitative chemical screening of the sponge extracts was conducted by using standard methods while the total phenolic content (TPC was estimated through the Folin-Ciocalteu method. Antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli and Proteus mirabilis. The minimum inhibitory concentration was determined by the broth microdilution method. All sponge extracts were assessed for antioxidant activity via the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging in vitro model. Results: Alkaloids, phenols, steroids, terpenoids, tannins and saponins were detected in the sponge extracts and TPC varied from (2.280±0.072 mg to (12.790±0.236 mg gallic acid equivalents per gram extract (P<0.05. All the extracts inhibited the growth of at least two bacterial strains whilst the most potent in vitro antibacterial activities were observed in the most polar ethyl acetate and butanol fractions (minimum inhibitory concentration values 0.103–0.211 mg/mL of P. nigra. Each extract scavenged 1,1-diphenyl-2-picrylhydrazyl free radicals while the hexane fraction displayed the highest scavenging ability at (27.50±1.85% (P<0.05. Antioxidant activity was positively correlated with TPC (R2 =0.843. Contrary relationships were also found between antibacterial activity and TPC. Conclusions: The present study validates the antioxidant and antibacterial activity of marine sponge (P. nigra extracts and depicts the sea sponge as a potential source of pharmaceutical leads against infectious and degenerative diseases.

  11. The stability of rutin and chlorogenic acid during the processing of black elder (Sambucus nigra) inflorescence

    Czech Academy of Sciences Publication Activity Database

    Dadáková, E.; Vrchotová, Naděžda; Chmelová, Š.; Šerá, Božena

    2011-01-01

    Roč. 40, č. 3 (2011), s. 327-334 ISSN 0139-3006 R&D Projects: GA ČR(CZ) GA525/05/2546 Institutional research plan: CEZ:AV0Z60870520 Keywords : black elder * Sambucus nigra L * rutin * chlorogenic acid * high-performance liquid chromatography * micellar electrokinetic chromatography Subject RIV: GM - Food Processing Impact factor: 0.444, year: 2011

  12. Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Ibrahim Turan

    2017-02-01

    Full Text Available Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3 cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC, ferric reducing antioxidant power (FRAP and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

  13. Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells.

    Science.gov (United States)

    Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Burnaz, Nesibe Arslan; Yaman, Serap Ozer; Akbulut, Kubra; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, Orhan

    2017-02-01

    Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G 1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

  14. Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae)

    OpenAIRE

    G. R. Souza; R. G. Oliveira-Junior; T. C. Diniz; A. Branco; S. R. G. Lima-Saraiva; A. L. Guimarães; A. P. Oliveira; A. G. M. Pacheco; M. G. Silva; M. O. Moraes-Filho; M. P. Costa; C. Ó. Pessoa; J. R. G. S. Almeida

    2017-01-01

    Abstract This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents we...

  15. Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

    Science.gov (United States)

    Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan

    2016-04-01

    One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Wood identification of Dalbergia nigra (CITES Appendix I) using quantitative wood anatomy, principal components analysis and naive Bayes classification.

    Science.gov (United States)

    Gasson, Peter; Miller, Regis; Stekel, Dov J; Whinder, Frances; Zieminska, Kasia

    2010-01-01

    Dalbergia nigra is one of the most valuable timber species of its genus, having been traded for over 300 years. Due to over-exploitation it is facing extinction and trade has been banned under CITES Appendix I since 1992. Current methods, primarily comparative wood anatomy, are inadequate for conclusive species identification. This study aims to find a set of anatomical characters that distinguish the wood of D. nigra from other commercially important species of Dalbergia from Latin America. Qualitative and quantitative wood anatomy, principal components analysis and naïve Bayes classification were conducted on 43 specimens of Dalbergia, eight D. nigra and 35 from six other Latin American species. Dalbergia cearensis and D. miscolobium can be distinguished from D. nigra on the basis of vessel frequency for the former, and ray frequency for the latter. Principal components analysis was unable to provide any further basis for separating the species. Naïve Bayes classification using the four characters: minimum vessel diameter; frequency of solitary vessels; mean ray width; and frequency of axially fused rays, classified all eight D. nigra correctly with no false negatives, but there was a false positive rate of 36.36 %. Wood anatomy alone cannot distinguish D. nigra from all other commercially important Dalbergia species likely to be encountered by customs officials, but can be used to reduce the number of specimens that would need further study.

  17. Determination of Antioxidant Activity and Toxicity of Sambucus nigra Fruit Extract Using Alternative Methods

    Directory of Open Access Journals (Sweden)

    Elena Doroftei

    2012-01-01

    Full Text Available The aim of the study is to measure the in vitro antioxidant activity of elderberry (Sambucus nigra fruit extract and to study its toxicity in a plant model system with regard to its possible application in food and agricultural industry. The antioxidant capacity of Sambucus nigra fruit powder was quantified by a photochemiluminescence method. The study of phytotoxicity of aqueous solutions of powder extract was performed using Allium cepa as a test organism. Photochemiluminescence determinations showed a very high antioxidant capacity of the product but also revealed its cytotoxic effect, along with mitodepressive activity and even inhibiton of mitosis at the preprophase stage when the fruit extract was used at higher concentrations. Aqueous solutions of the fruit powder have a reasonably expressed mutagenic activity in vivo on the radicles of Allium cepa, especially when they are used at a concentration of 1 g/dL for a prolonged time (48 h. At lower concentrations (0.1 g/dL, however, the mutagenic effect was not observed any more. The conclusion of our study is that Sambucus nigra fruit extract powder has a very high in vitro antioxidant activity and no mutagenic effects at low concentrations, which makes it recommendable for applications in the food industry.

  18. Quali-quantitative analyses of Flavonoids of Morus nigra L. and Morus alba L. (Moraceae) fruits.

    Science.gov (United States)

    Pawlowska, Agata Maria; Oleszek, Wieslaw; Braca, Alessandra

    2008-05-14

    Morus nigra L., belonging to the Moraceae family, is a decidious tree widely cultivated in Europe and West Asia. It has a long history of medicinal use in Chinese medicine, as a remedy for many kinds of diseases. The aim of the present study was to evaluate the profile of the phenolic constituents of M. nigra fruits and to compare their content with the fruits of another species of Morus, Morus alba, which is also very well known in folklore medicine. The fruits of black and white mulberries have been studied, and five compounds from the methanol extract have been identified by means of HPLC/PDA/ESI-MS. Four compounds (quercetin 3- O-glucoside, quercetin 3- O-rutinoside, kaempferol 3- O-rutinoside, and 5- O-caffeoylquinic acid) have been isolated by use of Sephadex LH-20 column chromatography and HPLC and characterized by means of NMR and ESI-MS. Furthermore, HPLC/PDA/ESI-MS analysis of the red pigment of M. nigra fruits revealed the presence of four anthocyanins recognized as cyanidin 3- O-glucoside, cyanidin 3- O-rutinoside, pelargonidin 3- O-glucoside, and pelargonidin 3- O-rutinoside. All of the compounds were quantified.

  19. Bioassay-Guided Isolation and Characterization of Wound Healer Compounds from Morus nigra L. (Moraceae

    Directory of Open Access Journals (Sweden)

    Esra Küpeli Akkol

    2015-04-01

    Full Text Available Leaves and fruits of Morus nigra L. (Moraceae are used for the treatment of wounds especially mouth sore in Turkish traditional medicine. The present study was designed to investigate wound healing activity of M. nigra by using incision and excision wound models. Furthermore, anti-inflammatory activity was assessed by Whittle method. Lyophilized fruit extract (MNF displayed significant wound healing activity, while aqueous leaf extract of M. nigra (MNL did not. Through biological activity guided fractionation technique, MNF was subjected to successive solvent extraction. Among the subextracts obtained, n-butanol (MNF-n-BuOH subextract was found to possess wound healing activity. MNF -n-BuOH was subjected Sephadex LH-20 column chromatography to obtain three fractions, which then applied to the same biological activity tests. Compounds 1 and 2 were isolated from the active fraction and their structures were identified as quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside, respectively. The isolates were investigated for their in vitro enzyme inhibitory activities.

  20. EVALUATION OF ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY OF LEAF TEAS BLACKBERRY (MORUS NIGRA

    Directory of Open Access Journals (Sweden)

    P. Zanco

    2017-02-01

    Full Text Available Brazil has a long tradition in the use of plants, and is the same used in different ways, such as in the form of infusions and decoctions, for therapeutic purposes. Morus nigra species is a plant that has been used in different parts of the world as phytotherapy. This plant is known as mulberry, black, blackberry black or blackberry and various parts of the plant, such as leaves, fruit, bark and roots are used by the population, demonstrating anti-inflammatory activity, antioxidant, hypoglycemic, antimicrobial, among others. Because of the interest in research on the bioactivity of plant products and use of blackberry tea in the population, present study evaluated the antibacterial activity of teas M. nigra leaves obtained by infusion and decoction against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium, as well as the antioxidant potential of preparations by DPPH technique. Results revealed that the infusions and decoctions prepared with Morus nigra leaves showed no ability to inhibit the growth of bacteria tested. However, all preparations (decoctions and infusions obtained from the leaves showed antioxidant potential, demonstrated ability to reduce DPPH radical. Despite infusions and decoctions evaluated in this study do not show antimicrobial activity, both had significant antioxidant property. Considering the use of different plants, including mulberry tree, by the people, it is considered always important proof of their biological activities.

  1. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products.

    Science.gov (United States)

    Porter, Randall S; Bode, Robert F

    2017-04-01

    Black elder (Sambucus nigra L.) has a long ethnobotanical history across many disparate cultures as a treatment for viral infection and is currently one of the most-used medicinal plants worldwide. Until recently, however, substantial scientific research concerning its antiviral properties has been lacking. Here, we evaluate the state of current scientific research concerning the use of elderberry extract and related products as antivirals, particularly in the treatment of influenza, as well as their safety and health impacts as dietary supplements. While the extent of black elder's antiviral effects are not well known, antiviral and antimicrobial properties have been demonstrated in these extracts, and the safety of black elder is reflected by the United States Food and Drug Administration approval as generally recognized as safe. A deficit of studies comparing these S. nigra products and standard antiviral medications makes informed and detailed recommendations for use of S. nigra extracts in medical applications currently impractical. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

    International Nuclear Information System (INIS)

    Gonzales-Lima, F.

    1986-01-01

    The autoradiographic ( 14 C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. (author)

  3. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model.

    Science.gov (United States)

    Lazzarini, Marcio; Martin, Sabine; Mitkovski, Mišo; Vozari, Rita Raisman; Stühmer, Walter; Bel, Elaine Del

    2013-07-01

    Neuron-glia interactions play a key role in maintaining and regulating the central nervous system. Glial cells are implicated in the function of dopamine neurons and regulate their survival and resistance to injury. Parkinson's disease is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, decreased striatal dopamine levels and consequent onset of extrapyramidal motor dysfunction. Parkinson's disease is a common chronic, neurodegenerative disorder with no effective protective treatment. In the 6-OHDA mouse model of Parkinson's disease, doxycycline administered at a dose that both induces/represses conditional transgene expression in the tetracycline system, mitigates the loss of dopaminergic neurons in the substantia nigra compacta and nerve terminals in the striatum. This protective effect was associated with: (1) a reduction of microglia in normal mice as a result of doxycycline administration per se; (2) a decrease in the astrocyte and microglia response to the neurotoxin 6-OHDA in the globus pallidus and substantia nigra compacta, and (3) the astrocyte reaction in the striatum. Our results suggest that doxycycline blocks 6-OHDA neurotoxicity in vivo by inhibiting microglial and astrocyte expression. This action of doxycycline in nigrostriatal dopaminergic neuron protection is consistent with a role of glial cells in Parkinson's disease neurodegeneration. The neuroprotective effect of doxycycline may be useful in preventing or slowing the progression of Parkinson's disease and other neurodegenerative diseases linked to glia function. Copyright © 2013 Wiley Periodicals, Inc.

  4. Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward.

    Science.gov (United States)

    Pujara, Maia S; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2016-05-04

    The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the "reward circuit" of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited "reward circuit," the ventral striatum and the ventromedial prefrontal

  5. BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

    Science.gov (United States)

    Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

    2016-09-01

    According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

  6. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

    Science.gov (United States)

    Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko

    2015-01-01

    Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT, GABA and bone marrow cell supplementation

    Directory of Open Access Journals (Sweden)

    Romeo Chinthu

    2011-01-01

    Full Text Available Abstract Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P

  9. Fungi inhabiting stumps of Pinus nigra depending on the period of their exposure

    Directory of Open Access Journals (Sweden)

    Robert Jankowiak

    2014-08-01

    Full Text Available The purpose of this study was to determine the species composition of communities of fungi inhabiting stumps of Pinus nigra depending on the period of their exposure. After 6 and 18 months of stump exposure two species of Basidiomycota distinctly dominaled: Stereum sanguinolentum and Phanerochaete gigantea. After 30 months of exposure the communities of fungi were the most diversified. A longer period of stump exposure resulted in the decrease of numbers of isolates of Ph. gigantea and S. sanguinolentum. However, other species belonging to Basidiomycota increased their numbers. As the wood decompositionn progressed, however, the fungi belonging to Deuteromycota were isolated more often.

  10. Evaluation of hypoglycemic potential and pre-clinical toxicology of Morus nigra L. (Moraceae)

    OpenAIRE

    Quintans Júnior, Lucindo José; Sá, Pedro G. S. de; Oliveira, Roniere A. de; Neves, Leonardo F.; Silva, Fabrício S.; Araújo, Edigênia C. da C.; Oliveira, Ana P. de; Guimarães, Amanda L.; Silva Almeida, Jackson R. G. da

    2011-01-01

    The hypoglycemic potential of crude ethanolic extract of leaves (CEE-Mn) of the Morus nigra L. (Moraceae) was evaluated in normoglycemic rats. CEE-Mn (200 and 400 mg/kg) and metformin (500 mg/kg) were tested on the glucose tolerance oral test. The acute toxicity of CEE-Mn was performed 2.0 g/kg intraperitoneally and 5.0 g/kg orally in Swiss mice. Blood was removed after seven days for laboratory analysis of hematological and biochemical parameters. In the glucose tolerance oral te...

  11. Estudo farmacobotânico das folhas de amoreira-preta, Morus nigra L., Moraceae

    OpenAIRE

    Padilha, Marina M.; Moreira, Lucimara Q.; Morais, Fernanda F.; Araújo, Tomáz. H.; Alves-da-Silva, Geraldo

    2010-01-01

    Morus nigra L., Moraceae, é uma espécie pertencente à família Moraceae, conhecida comumente como amoreira-preta. Na medicina popular é empregada nos casos de ondas de calor e até mesmo indicada como terapia de reposição hormonal. Possui atividade antioxidante, hipoglicemiante, antiinflamatória e antimicrobiana. O presente trabalho trata da caracterização estrutural da folha, de modo a contribuir na morfodiagnose para o controle de qualidade. Amostras do material vegetal foram seccionadas, fix...

  12. Stable Encoding of Task Structure Coexists With Flexible Coding of Task Events in Sensorimotor Striatum

    Science.gov (United States)

    Kubota, Yasuo; Liu, Jun; Hu, Dan; DeCoteau, William E.; Eden, Uri T.; Smith, Anne C.

    2009-01-01

    The sensorimotor striatum, as part of the brain's habit circuitry, has been suggested to store fixed action values as a result of stimulus-response learning and has been contrasted with a more flexible system that conditionally assigns values to behaviors. The stability of neural activity in the sensorimotor striatum is thought to underlie not only normal habits but also addiction and clinical syndromes characterized by behavioral fixity. By recording in the sensorimotor striatum of mice, we asked whether neuronal activity acquired during procedural learning would be stable even if the sensory stimuli triggering the habitual behavior were altered. Contrary to expectation, both fixed and flexible activity patterns appeared. One, representing the global structure of the acquired behavior, was stable across changes in task cuing. The second, a fine-grain representation of task events, adjusted rapidly. Such dual forms of representation may be critical to allow motor and cognitive flexibility despite habitual performance. PMID:19625536

  13. Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

    Science.gov (United States)

    Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

    2011-05-01

    Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  14. Curvularia microspora sp. nov. associated with leaf diseases of Hippeastrum striatum in China

    Directory of Open Access Journals (Sweden)

    Yin Liang

    2018-01-01

    Full Text Available An undescribed Curvularia sp. was isolated from the leaf spot disease of Barbados Lily (Hippeastrum striatum (Lam. Moore. Phylogenetic analyses of combined ITS, 28S, GPD1 and TEF1 sequence data place nine strains of this species in the trifolii-clade, but they clustered together as an independent lineage with strong support. This species was morphologically compared with related species in the trifolii-clade. Based on differences in morphology and phylogeny, it is concluded that this species is a new taxon, introduced as Curvularia microspora sp. nov. Pathogenicity testing determined the new species to be pathogenic on H. striatum.

  15. The subspecific characters and distribution of the New World Skimmers - Rynchops nigra The subspecific characters and distribution of the New World Skimmers - Rynchops nigra

    Directory of Open Access Journals (Sweden)

    Wetmore Alexander

    1944-09-01

    Full Text Available The distribution of the forms of the New World rayador, or skimmer, Rynchops nigra, and the characters that mark the geographic races, have been matters of interest to me for a number of years, an interest heightened by recent discussions in current literature of the identity of the birds found on the Pacific coast of Mexico, and far to the south in Chile. Investigation into these matters with the material available in the National Museum not being conclusive, specimens from Mexico and the West Indies southward to Argentina and Chile in other large collections in the United states have been assembled through the courtesy of Dr. Robert Cushman Murphy of the American Museum of Natural History, James l.. Peters of the Museum of Comparative Zoology,W. E. C. Todd of the Carnegie Museum, and Dr. Karl P. Schmidt of the Field Museum of Natural History. I have also to thank Dr. Alden H. Miller for the use of one specimen from Chubut in the Museum of Vertebrate Zoology, and Dean Amadon for certain notes on this group of birds that he had assembled.The distribution of the forms of the New World rayador, or skimmer, Rynchops nigra, and the characters that mark the geographic races, have been matters of interest to me for a number of years, an interest heightened by recent discussions in current literature of the identity of the birds found on the Pacific coast of Mexico, and far to the south in Chile. Investigation into these matters with the material available in the National Museum not being conclusive, specimens from Mexico and the West Indies southward to Argentina and Chile in other large collections in the United states have been assembled through the courtesy of Dr. Robert Cushman Murphy of the American Museum of Natural History, James l.. Peters of the Museum of Comparative Zoology,W. E. C. Todd of the Carnegie Museum, and Dr. Karl P. Schmidt of the Field Museum of Natural History. I have also to thank Dr. Alden H. Miller for the use of one specimen

  16. Morphometric analysis of neurons from the marginal and substantia gelatinosa layers of human spinal cord: Classification according to laminar organization

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    Milošević Nebojša T.

    2005-01-01

    Full Text Available The main goal of morphometric analysis of neuronal images, except for getting information about their geometry and dendritic branching patterns, is their classification based on laminar organization. The majority of contemporary techniques for image analysis are based on the application of fractal theory, which has some limitations on results analysis. For that reasons, the new, mostly nonfractal techniques for image analysis had been designed in the past few years. This study shows the analysis of morphometry of the human spinal cord neurons from the marginal (lamina I and substantia gelatinosa (laminae I-II. For the analysis of neuron images two techniques of morphometric analysis were used: box-counting method as a mainly used technique for fractal analysis, and circle-counting method as a newly designed technique for measuring the length of dendrites. The use of these methods for neurons of the mentioned regions of human spinal cord showed that circlecounting method had given more accurate results than fractal analysis method. When the proposed method was used for the analysis of neuronal images, it was possible to classify neurons according to their laminar position.

  17. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Directory of Open Access Journals (Sweden)

    Thi Thanh Hoang Nguyen

    2013-01-01

    Full Text Available The substantia gelatinosa (SG of the trigeminal subnucleus caudalis (Vc has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM and almost completely blocked by strychnine (2 μM, suggesting that taurine-mediated responses are via glycine receptor (GlyR activation. In addition, taurine (1 mM activated extrasynaptic GABAA receptor (GABAAR-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons.

  18. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Han, Seong Kyu

    2013-01-01

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC) with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM) showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM) and almost completely blocked by strychnine (2 μM), suggesting that taurine-mediated responses are via glycine receptor (GlyR) activation. In addition, taurine (1 mM) activated extrasynaptic GABAA receptor (GABAAR)-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons. PMID:24379976

  19. Canopy treatment influences growth of replacement tree species in Fraxinus nigra forests threatened by the emerald ash borer in Minnesota, USA

    Science.gov (United States)

    Christopher E. Looney; Anthony W. D' Amato; Brian J. Palik; Robert A. Slesak

    2017-01-01

    Fraxinus nigra Marsh. (black ash), a dominant tree species of wetland forests in northern Minnesota, USA, is imperiled by the invasive insect emerald ash borer (EAB; Agrilus planipennis Fairmaire, 1888). Regeneration of associated tree species is generally low in F. nigra forests and could be impacted...

  20. Atividade antinociceptiva do extrato etanólico das folhas de Morus nigra L. (Moraceae

    Directory of Open Access Journals (Sweden)

    Grasielly Rocha Souza

    2015-09-01

    Full Text Available O extrato etanólico bruto das folhas de M. nigra (Mn-EtOH foi avaliado quanto à atividade antinociceptiva em modelos experimentais em camundongos. Foram usados os métodos de contorções abdominais induzidas pelo ácido acético, teste da formalina e placa quente. No teste de contorções abdominais induzidas pelo ácido acético, Mn-EtOH (100, 200 e 400 mg/kg, i.p. reduziu o número de contorções em 38,82, 97,65 e 100%, respectivamente. O extrato também produziu uma significativa inibição de ambas as fases do teste da formalina, sendo que o efeito foi mais significativo na segunda fase (dor inflamatória. O extrato diminuiu em 42,19, 56,96 e 40,50%, respectivamente, o tempo de lambida da pata na primeira fase do teste de formalina, assim como 84,04, 77,20 e 61,07%, respectivamente, na segunda fase. Além disso, não apresentou efeito no teste da placa quente. Os dados obtidos sugerem que o extrato tem efeito antinociceptivo, provavelmente mediado através de mecanismos periféricos. Novos estudos estão sendo realizados para caracterizar o mecanismo responsável por esse efeito.Palavras-chave: Morus nigra. Moraceae. Atividade antinociceptiva. Dor. ABSTRACTAntinociceptive activity of ethanolic extract of the leaves of Morus nigra L. (MoraceaeThe crude ethanolic extract of the leaves of M. nigra (Mn-EtOH was evaluated for antinociceptive activity in mice using models of nociception. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests. In the acetic acid-induced writhing test, the Mn-EtOH (100, 200 and 400 mg/kg, i.p. reduced the number of writhing by 38.82, 97.65 and 100%, respectively. The extract also produced a significant inhibition of both phases of the formalin test, and the effect was more significant in the second phase (inflammatory pain. The extract decreased by 42.19, 56.96 and 40.50%, respectively, the paw licking time in the first phase of

  1. Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

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    Pamphyle Abedi Mukutenga

    2012-08-01

    Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

  2. Human Dorsal Striatum Encodes Prediction Errors during Observational Learning of Instrumental Actions

    Science.gov (United States)

    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…

  3. Materials as regard about ecology and spreading of lycodine striatum bicolor nik in Tajikistan

    International Nuclear Information System (INIS)

    Sattorov, T.S.; Khidirov, Kh.; Mukhammadkulov, M.

    2003-01-01

    In this article is placed new scientific information about biology, ecology and spreading of Lycodine striatum bicolor within the territory of Tajikistan. Finding available in this article concerning spreading of flus snake are considered to be new. This scarce snake was discovered for the first time in Northern part of Tajikistan. This new information will enrich our notions about Reptile fauna of Tajikistan

  4. Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

    Directory of Open Access Journals (Sweden)

    Kevin D. Alloway

    2017-07-01

    Full Text Available The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD and related neurological disorders.

  5. Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernandez, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  6. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernández, G.

    2017-01-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  7. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

    NARCIS (Netherlands)

    Vogel, Susanne; Klumpers, Floris; Schroeder, Tobias Navarro; Oplaat, Krista T.; Krugers, Harm J.; Oitzl, Melly S.; Joels, Marian; Doeller, Christian F.; Fernandez, Guillen

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

  8. Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior

    NARCIS (Netherlands)

    van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.

    2014-01-01

    Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and

  9. Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

    Science.gov (United States)

    Baker, Phillip M.; Ragozzino, Michael E.

    2014-01-01

    Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

  10. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

    NARCIS (Netherlands)

    Holz, N.E.; Boecker-Schlier, R.; Buchmann, A.F.; Blomeyer, D.; Jennen-Steinmetz, C.; Baumeister, S.; Plichta, M.M.; Cattrell, A.; Schumann, G.; Esser, G.; Schmidt, M.; Buitelaar, J.K.; Meyer-Lindenberg, A.; Banaschewski, T.; Brandeis, D.; Laucht, M.

    2017-01-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At

  11. [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

    Science.gov (United States)

    Liu, Ping; He, Xinrong; Guo, Mei

    2010-04-01

    To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

  12. The role of the dorsoanterior striatum in implicit motivation: The case of the need for power

    Directory of Open Access Journals (Sweden)

    Oliver C Schultheiss

    2013-04-01

    Full Text Available Implicit motives like the need for power (nPower scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions in behavioral studies and (b activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2, 217-222 model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.

  13. Fast and robust segmentation of the striatum using deep convolutional neural networks.

    Science.gov (United States)

    Choi, Hongyoon; Jin, Kyong Hwan

    2016-12-01

    Automated segmentation of brain structures is an important task in structural and functional image analysis. We developed a fast and accurate method for the striatum segmentation using deep convolutional neural networks (CNN). T1 magnetic resonance (MR) images were used for our CNN-based segmentation, which require neither image feature extraction nor nonlinear transformation. We employed two serial CNN, Global and Local CNN: The Global CNN determined approximate locations of the striatum. It performed a regression of input MR images fitted to smoothed segmentation maps of the striatum. From the output volume of Global CNN, cropped MR volumes which included the striatum were extracted. The cropped MR volumes and the output volumes of Global CNN were used for inputs of Local CNN. Local CNN predicted the accurate label of all voxels. Segmentation results were compared with a widely used segmentation method, FreeSurfer. Our method showed higher Dice Similarity Coefficient (DSC) (0.893±0.017 vs. 0.786±0.015) and precision score (0.905±0.018 vs. 0.690±0.022) than FreeSurfer-based striatum segmentation (p=0.06). Our approach was also tested using another independent dataset, which showed high DSC (0.826±0.038) comparable with that of FreeSurfer. Comparison with existing method Segmentation performance of our proposed method was comparable with that of FreeSurfer. The running time of our approach was approximately three seconds. We suggested a fast and accurate deep CNN-based segmentation for small brain structures which can be widely applied to brain image analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

    Science.gov (United States)

    Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

    2016-12-14

    Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

  15. Seed development in Phaseolus vulgaris L., Populus nigra L., and Ranunculus sceleratus L. with special reference to the microtubular cytoskeleton

    NARCIS (Netherlands)

    XuHan, X.

    1995-01-01

    In this thesis, seed development is investigated in celery-leafed buttercup ( Ranunculus sceleratus L.), bean ( Phaseolus vulgaris L.) and poplar ( Populus nigra L.). Developing embryos, endosperms and seed coats are

  16. Development of a reliable method for determining sex for a primitive rodent, the Point Arena mountain beaver (Aplodontia rufa nigra)

    Science.gov (United States)

    Kristine L. Pilgrim; William J. Zielinski; Fredrick V. Schlexer; Michael K. Schwartz

    2012-01-01

    The mountain beaver (Aplodontia rufa) is a primitive species of rodent, often considered a living fossil. The Point Arena mountain beaver (Aplodontia rufa nigra) is an endangered subspecies that occurs in a very restricted range in northern California. Efforts to recover this taxon have been limited by the lack of knowledge on their demography, particularly sex and age...

  17. Isoprenylated flavonoids from Morus nigra and their PPAR γ agonistic activities.

    Science.gov (United States)

    Xu, Liang-Jin; Yu, Mei-Hua; Huang, Chun-Yue; Niu, Li-Xin; Wang, Yi-Fan; Wu, Chun-Zhen; Yang, Pei-Ming; Hu, Xiao

    2018-02-08

    A novel dihydroflavonol unprecedentedly with a prenyl group at C-2, nigragenon A (1), four new sanggenon-type flavonones, nigragenons B-E (2-5), along with six known isoprenylated flavonoids (6-11) were isolated from the twigs of Morus nigra. Their structures were elucidated through extensive analysis of spectroscopic data. Interestingly, compound 1 was the first reported biogenetic precursor of sanggenon-type flavanones and the biogenetic pathway from 1 to sanggenol F was proposed. The PPAR γ agonistic activity was investigated in HEK293 cells using dual luciferase reporter assay. Compounds 2, 4, 7, and 9 showed obvious agonistic activities on PPAR γ, and compound 2 was a potential PPAR γ partial agonist. Moreover, the preliminary structure-activity relationships for the tested compounds were discussed. Copyright © 2018. Published by Elsevier B.V.

  18. Effects of water stress on germination of Pinus nigra Arnold. seeds

    International Nuclear Information System (INIS)

    Topacoglu, O.; Sevik, H.; Akkuzu, E.

    2016-01-01

    Climate change, global warming and the deterioration of related environmental conditions cause an important problem for forest tree species. For this reason, it is necessary to determine the response of trees to these conditions. The Objective of this study was to investigate the effects of water stress on seed germination of fifteen Pinus nigra Arnold. provenances in Turkey. For this purpose, the water stresses between 0 and -8.0 bars were obtained using polyethylene glycol-6000 (PEG) solutions. Seeds were kept for 35 days at 20 ± 0.5 degree C. In this study, significant variations between the provenances were found. Ankara Uluhan ( percent 95, 08) and Isparta Tota ( percent 85, 41) provenances at -8.0 bars having the highest cumulative germination percentages were the most resistant provenances against the water stress. This study has shown that the water stress reduced the germination speed, germination percentage and germination value. (author)

  19. Estudo farmacobotânico das folhas de amoreira-preta, Morus nigra L., Moraceae

    Directory of Open Access Journals (Sweden)

    Marina M. Padilha

    Full Text Available Morus nigra L., Moraceae, é uma espécie pertencente à família Moraceae, conhecida comumente como amoreira-preta. Na medicina popular é empregada nos casos de ondas de calor e até mesmo indicada como terapia de reposição hormonal. Possui atividade antioxidante, hipoglicemiante, antiinflamatória e antimicrobiana. O presente trabalho trata da caracterização estrutural da folha, de modo a contribuir na morfodiagnose para o controle de qualidade. Amostras do material vegetal foram seccionadas, fixadas e coradas com fucsina e toluidina. A folha apresenta estômatos anomocíticos na face abaxial, tricomas tectores, mesofilo bifacial, drusas, nervura central semi-convexa e o pecíolo exibe feixes vasculares em arco fechado.

  20. Pre-clinical toxicological evaluation of tea from the leaves of Morus nigra L. (Moraceae)

    OpenAIRE

    Oliveira, A.C.B.; Oliveira, A.P.; Guimarães, A.L.; Oliveira, R.A.; Silva, F.S.; Reis, S.A.G.B.; Ribeiro, L.A.A.; Almeida, J.R.G.S.

    2013-01-01

    O objetivo desse estudo foi realizar um ensaio toxicológico pré-clínico para analisar a toxicidade do chá das folhas de Morus nigra L. (Moraceae). A toxicidade subcrônica do chá (CF-Mn) foi avaliada durante 30 dias por via oral em ratos. Ao grupo controle foi administrado água, para comparação. Durante o período experimental foi avaliada a presença de sinais de toxicidade, variação do peso corporal, e o consumo de líquido e alimento. Ao final do experimento o sangue dos animais foi retirado p...

  1. Rhabdomyosarcoma in a terrestrial tortoise (Geochelone nigra in Nigeria: A case report

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    Oghenemega D. Eyarefe

    2012-11-01

    Full Text Available A skeletal muscle tumour (rhabdomysarcoma was diagnosed in a 4-year-old captive female terrestrial tortoise (Geochelone nigra weighing 7 kg presented at the Veterinary Teaching Hospital, University of Ibadan, Ibadan, Nigeria. The tumour was located at the anterior right portion of the body and ventral to the carapace. The location of the tumour prevented the tortoise from extending its head from the body. The tumour was a sessile, smooth white mass, with a soft myxomatous consistency. The histological features that were diagnostic of rhabdomyosarcoma included a sparse population of haphazardly arranged spindle-shaped cells within a homogenous matrix (anisocytosis, occasional tumour giant and binucleate cells, and some well differentiated myofibrils with cross striations within the cytoplasm. The paucity of information on tumours in the land tortoise was the reason for this report, which appears to be the first report of rhabdomyosarcoma in the tortoise.

  2. Agromyces ulmi sp. nov., a xylanolytic bacterium isolated from Ulmus nigra in Spain.

    Science.gov (United States)

    Rivas, Raúl; Trujillo, Martha E; Mateos, Pedro F; Martínez-Molina, Eustoquio; Velázquez, Encarna

    2004-11-01

    Two xylan-degrading bacterial strains were isolated from a decayed Ulmus nigra tree in Spain. The isolates were Gram-positive, non-motile, aerobic and formed substrate mycelium which fragmented into irregular rods. 16S rRNA gene sequence analysis indicated that the isolates form a separate branch within the genus Agromyces phylogenetic cluster, with Agromyces mediolanus DSM 20152(T) being their closest relative (97.7 and 97.6 % sequence similarity). Catalase, nitrate reduction and urease tests differentiated these strains from A. mediolanus. Cell-wall peptidoglycan composition, major menaquinone, predominant fatty acids and phospholipid pattern were typical of the genus Agromyces. The DNA G+C content determined for the type strain XIL01(T) was 72 mol%. Based on the data presented, a novel species Agromyces ulmi sp. nov. is proposed. The type strain is XIL01(T) (=LMG 21954(T)=DSM 15747(T)).

  3. Fermentation of an Aromatized Wine-Based Beverage with Sambucus nigra L. Syrup (after Champenoise Method

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    Teodora Emilia Coldea

    2015-11-01

    Full Text Available The sparkling wine based beverage with elderflower (Sambucus nigra L. syrup presented improved sensorial characteristics. White wine used was Fetească regală variety, obtained in Micro winery of University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca. Elderflower syrup was prepared without thermal treatment, but was pasteurised before its addition to wine. Elderflower have many health benefits, such as diuretic, diaphoretic, or antioxidant activity. In this study it was used elderflower syrup both to improve the product s sensorial properties, and for their multiple benefits to health. The sparkling wine based beverage with elderflower syrup was produced by fermentation in the bottle (after Champenoise method, with the addition of wine yeast. The novelty brought by this paper is the use of elderflower syrup in alcoholic-beverage industry.

  4. Rhabdomyosarcoma in a terrestrial tortoise (Geochelone nigra) in Nigeria: a case report.

    Science.gov (United States)

    Eyarefe, Oghenemega D; Antia, Richard E; Oguntoye, Cecilia O; Abiola, Olusoji O; Alaka, Olugbenga O; Ogunsola, John O

    2012-11-30

    A skeletal muscle tumour (rhabdomysarcoma) was diagnosed in a 4-year-old captive female terrestrial tortoise (Geochelone nigra) weighing 7 kg presented at the Veterinary Teaching Hospital, University of Ibadan, Ibadan, Nigeria. The tumour was located at the anterior right portion of the body and ventral to the carapace. The location of the tumour prevented the tortoise from extending its head from the body. The tumour was a sessile, smooth white mass, with a soft myxomatous consistency. The histological features that were diagnostic of rhabdomyosarcoma included a sparse population of haphazardly arranged spindle-shaped cells within a homogenous matrix (anisocytosis), occasional tumour giant and binucleate cells, and some well differentiated myofibrils with cross striations within the cytoplasm. The paucity of information on tumours in the land tortoise was the reason for this report, which appears to be the first report of rhabdomyosarcoma in the tortoise.

  5. Microfungi found on phellen of Jugulans nigra L. in Southeastern Ohio, USA

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    Emanuel D. Rudolph

    2014-01-01

    Full Text Available Bark surfaces from black walnut (Jugulans nigra trees of three sites in southeastern Ohio, half. Five. and ten miles from the Ohio River, were used in late autumn to isolate fungi in culture. as well as to search for the presence of fungal mycelium and spores. The pH of the cork also was determined. Fifty six, mostly cosmopolitan, species of microfungi and several yeasts were isolated, almost all belonging to imperfect form genera. with the largest number of species in the genus Penicillium. No relationship of fungal presence to cork pH was found among the sites whose acidity was related to closeness to the industrialized river edge. Relatively few fungi were isolated. and even fewer spores, and only four mycelia growths were found by electron microscopy. Several spores seen could not be matched with fungi that had been isolated. The bark seems to be a trapping surface for spores. rather than a place of fungal growth.

  6. Diversity and expression of nitrogenase genes (nifH) from ectomycorrhizas of Corsican pine (Pinus nigra).

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    Izumi, Hironari; Anderson, Ian C; Alexander, Ian J; Killham, Ken; Moore, Edward R B

    2006-12-01

    The diversity of bacterial nitrogenase genes (nifH) and their mRNA transcription in ectomycorrhizas of Corsican pine (Pinus nigra) were examined. DNA and RNA were extracted from surface-sterilized and non-sterilized Corsican pine roots colonized by the ectomycorrhizal (ECM) fungi, Suillus variegatus and Tomentellopsis submollis. DNA-derived nifH polymerase chain reaction (PCR) products were obtained from all samples, but only a few reverse transcription PCRs for nifH mRNA were successful, suggesting that nitrogenase genes were not always transcribed. Several different nifH sequences were detected and the bacteria actively transcribing nifH were different from those whose genes were detected through DNA-based PCR. Putative nitrogenase amino acid sequences revealed that more than half of the nifH products were derived from methylotrophic bacteria, such as Methylocella spp. The next most frequent sequence types were similar to those from Burkholderia.

  7. Preparation of a Kiln Drying Schedule for Poplar (Populus nigra Lumber of 5 cm Thickness

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    Sohrab Rahimi

    2011-12-01

    Full Text Available In order to establish a kiln drying schedule for Poplar (Populus nigra lumbers of 5 cm thickness commercially cut from Taleghan region, three schedules, namely T8-F4, T8-F5 and T9-F4 were adopted to dry the lumbers to the final moisture content of 11 ± 2%.  Dry bulb temperatures for the schedules were adjusted at 54, 54 and 60 °C, while the final dry-bulb temperatures were adjusted at 82, 82 and 71 °C, respectively. The severity of surface, internal checks and warp in the lumbers were measured before and after the drying process and quality control methods were used to analyze wood defects. Results indicated that drying of Poplar lumber using each of the three schedules was satisfactory; however, the third schedule (T9-F4 resulted in better drying quality than did the others. Also, equalizing of lumbers for 24h is recommended.

  8. Effect of ovarian tissue storage in Morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles

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    Agnes Yasmin Pitombeira Cavalcante

    2017-08-01

    Full Text Available This study demonstrated the effect of Morus nigra leaf extract during ovine ovarian tissue transportation on the survival and apoptosis of preantral follicles in vitro. High Performance Liquid Chromatography (HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract. Four pairs of ovaries from four sheep were collected. The ovarian cortex was fragmented and one fragment was fixed in 10% buffered formaldehyde and processed for histological and TUNEL analysis (fresh control. The other fragments were placed in Minimal Essential Medium (MEM – control medium or M. nigra extract (0.025; 0.05 or 0.1 mg/mL and stored (simulating transport at 4ºC for 6, 12 or 24 h. Preserved fragments (6 h were also destined to histological and TUNEL analysis. HPLC analysis confirmed the presence of antioxidant compounds (rutin, isoquercetin e kaempferitrin in the extract. There was a decrease (P 0.05 to 0.1 mg/mL of the extract. Apoptosis increased (P < 0.05 after conservation for 6 h in all treatments compared to the fresh control. Moreover, TUNEL positive cells decreased (P < 0.05 after preservation in 0.05 or 0.1 mg/mL M. nigra compared to MEM or 0.025 mg/mL M. nigra. In conclusion, 0.05 mg/mL M. nigra extract can be used as a preservation medium for ovine ovarian tissue at 4°C for up to 6 h.

  9. SAXS and other spectroscopic analysis of 12S cruciferin isolated from the seeds of Brassica nigra

    Science.gov (United States)

    Khaliq, Binish; Falke, Sven; Negm, Amr; Buck, Friedrich; Munawar, Aisha; Saqib, Maria; Mahmood, Seema; Ahmad, Malik Shoaib; Betzel, Christian; Akrem, Ahmed

    2017-06-01

    Oilseeds of the plant family Brassicaceae are important for providing both lipid and protein contents to human nutrition. Cruciferins (12S globulins) are seed storage proteins, which are getting attention due to their allergenic and pathogenicity related nature. This study describes the purification and characterization of a trimeric (∼190 kDa) cruciferin protein from the seeds of Brassica nigra (L.). Cruciferin was first partially purified by ammonium sulfate precipitation (30% saturation constant) and further purified by size exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82% sequence homology with cruciferin from Arabidopsis thaliana. The 50-55 kDa monomeric cruciferin produced multiple bands of two major molecular weight ranges (α-polypeptides of 28-32 kDa and β-polypeptides of 17-20 kDa) under reduced conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further separation of the bands into their isoforms with major pI ranges between 5.7 and 8.0 (α-polypeptides) and 5.5-8.5 (β-polypeptides). The Dynamic Light Scattering (DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of 5.8 ± 0.1 nm confirming the trimeric nature of the protein. The Circular Dichroism (CD) spectra showed both α-helices and β-sheets in the native conformation of the trimeric protein. The pure cruciferin protein (40 mg/ml) was successfully crystallized; however, the crystals diffracted only to low resolution data (8 Å). Small-angle x-ray scattering (SAXS) was applied to gain insights into the three-dimensional structure in solution. SAXS showed that the radius of gyration is 4.24 ± 0.25 nm and confirmed the nearly globular shape. The SAXS based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins.

  10. Genetic and morphological differentiation in Populus nigra L.: isolation by colonization or isolation by adaptation?

    Science.gov (United States)

    DeWoody, Jennifer; Trewin, Harriet; Taylor, Gail

    2015-06-01

    Identifying processes underlying the genetic and morphological differences among populations is a central question of evolutionary biology. Forest trees typically contain high levels of neutral genetic variation, and genetic differences are often correlated with geographic distance between populations [isolation by distance (IBD)] or are due to historic vicariance events [isolation by colonization (IBC)]. In contrast, morphological differences are largely due to local adaptation. Here, we examined genetic (microsatellite) and morphological (from a common garden experiment) variation in Populus nigra L., European black poplar, collected from 13 sites across western Europe and grown in a common garden in Belgium. Significant genetic differentiation was observed, with populations from France displaying greater admixture than the distinct Spanish and central European gene pools, consistent with previously described glacial refugia (IBC). Many quantitative traits displayed a bimodal distribution, approximately corresponding to small-leaf and large-leaf ecotypes. Examination of nine climatic variables revealed the sampling locations to have diverse climates, and although the correlation between morphological and climatic differences was significant, the pattern was not consistent with strict local adaptation. Partial Mantel tests based on multivariate summary statistics identified significant residual correlation in comparisons of small-leaf to large-leaf ecotypes, and within the small-leaf samples, but not within large-leaf ecotypes, indicating that variation within the small-leaf morphotype in particular may be adaptive. Some small-leaf populations experience climates very similar to those in large-leaf sites. We conclude that adaptive differentiation and persistent IBC acted in combination to produce the genetic and morphological patterns observed in P. nigra. © 2015 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  11. Gastroprotective Value of Berries: Evidences from Methanolic Extracts of Morus nigra and Rubus niveus Fruits

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    Luciane Angela Nottar Nesello

    2017-01-01

    Full Text Available This study evaluated the gastroprotective value of the methanol extracts from fruits of Morus nigra L. (black mulberry (MEMN and Rubus niveus Thunb (raspberry (MERN. The total phenolic compounds and flavonoids were measured, as well as the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH free radical scavenger activity. The gastroprotective effects of the extracts against 60% ethanol/0.3 M HCl were evaluated in mice. After that, the lipid hydroperoxides and reduced glutathione levels at ulcerated tissue were determined. The effects of extracts on H+/K+-ATPase activity were also verified. The extracts exhibited high contents of polyphenols; however, MERN presented 1.5-fold higher levels. The presence of flavonoids also was confirmed. In addition, MEMN (IC50 = 13.74 μg/mL and MERN (IC50 = 14.97 μg/mL scavenged DPPH radical. The MEMN reduced the ulcer area only at 300 mg/kg (p.o. by 64.06%. Interestingly, MERN decreased the ulcer area in a superior potency (ED50 = 20.88 mg/kg, reducing the ulcer area by 81.86% at 300 mg/kg, and increased the gastric mucin levels. The antioxidant effects of extracts were evidenced by reduced lipoperoxides and increased reduction of glutathione amount in the gastric mucosa. However, MEMN or MERN did not change the H+/K+-ATPase activity. These results confirm that M. nigra and R. niveus are berries with a gastroprotective value by strengthening of gastric protective factors.

  12. Acondicionamiento de reproductores, desove y cultivo larval de Graus nigra (Philippi, 1887 (Kyphosidae: Girellinae Broodstock conditioning, spawning and larval culture of Graus nigra (Philippi, 1887 (Kyphosidae: Girellinae

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    Avelino Muñoz

    2012-09-01

    Full Text Available Se describen resultados sobre acondicionamiento reproductivo, desove y cultivo larval de Graus nigra ("vieja negra", "mulata". Peces adultos silvestres se recolectaron y se utilizaron como reproductores, los que al final del período de acondicionamiento alcanzaron el estado de maduración gonadal y desovaron en forma natural y espontánea. Los huevos fueron recolectados y después de 36 h de incubación eclosionaron, con una tasa de eclosión promedio de 60%. Las larvas recién eclosionadas midieron 2,9 ± 0,23 mm y alcanzaron el día 50 post-eclosión (PE una longitud total de 12,6 ± 0,37 mm. La sobrevivencia larval posterior a la eclosión fue entre 50,9 y 79,1% y al día 30 PE fue de 12,1%. El cultivo larval se desarrolló en estanques con suministro de agua de mar filtrada y esterilizada. Después de la reabsorción del saco vitelino se produjo el desarrollo del tracto digestivo y las larvas se alimentaron con dieta viva enriquecida con emulsión de ácidos grasos altamente insaturados. A los 35 días de cultivo se ofreció alimento artificial a las larvas cuyo tamano fue aumentando progresivamente a medida que progresó su desarrollo ontogénico. Se describe la evolución anatómica de las larvas y las relaciones morfométricas que representan su desarrollo; se caracteriza el patrón de crecimiento de las larvas hasta los 50 días post-eclosión y se discuten aspectos relacionados con la sobrevivencia larval y la introducción de mejoras para optimizar la producción de larvas y juveniles.In this study results related to reproductive conditioning, spawning and larval culture of Graus nigra ("vieja negra", "mulata" are given. Wild adult fishes were collected and used as brooders which at the end of the conditioning period reached gonadal maturation state and spawned naturally and spontaneously. Eggs were collected and after 36 hours of incubation they hatched at average rate of 60%. The hatched larvae measured 2.9 ± 0.23 mm and at day 50

  13. Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

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    Miriam Matamales

    Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

  14. Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice.

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    Turgut, Nergiz Hacer; Mert, Derya Guliz; Kara, Haki; Egilmez, Hatice Reyhan; Arslanbas, Emre; Tepe, Bektas; Gungor, Huseyin; Yilmaz, Nese; Tuncel, Necati Baris

    2016-01-01

    Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. In extract, vanillic (632.093 μg/g) and chlorogenic acids (555.0 μg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.

  15. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

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    Silvana Vargas Superti

    2009-04-01

    Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

  16. SELEKSI RUMPUT LAUT Kappaphycus striatum DALAM UPAYA PENINGKATAN LAJU PERTUMBUHAN BIBIT UNTUK BUDIDAYA

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    Andi Parenrengi

    2017-01-01

    Full Text Available Budidaya rumput laut di Indonesia semakin berkembang seiring dengan peningkatan permintaan bahan baku industri untuk pasar domestik dan eksport. Rumput laut Kappaphycus striatum, salah satu spesies rumput laut komersil, telah intensif dibudidayakan di perairan pantai. Saat ini, masalah utama yang dihadapi pembudidaya adalah rendahnya kualitas bibit yang berasal dari hasil budidaya. Seleksi varietas merupakan salah satu metode yang diharapkan dapat meningkatkan laju pertumbuhan rumput laut. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh seleksi varietas terhadap pertumbuhan rumput laut sehingga dapat dilakukan produksi bibit unggul untuk keperluan budidaya. Budidaya rumput laut K. striatum telah dilakukan di Teluk Laikang, Kabupaten Takalar, Provinsi Sulawesi Selatan dengan menggunakan metode long line. Seleksi varietas dilakukan berdasarkan parameter laju pertumbuhan harian (LPH dan metode seleksi mengacu pada protokol seleksi yang telah dikembangkan pada rumput laut K. alvarezii. Hasil penelitian menunjukkan bahwa LPH bibit hasil seleksi lebih tinggi (P

  17. Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq

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    Ozgun Gokce

    2016-07-01

    Full Text Available The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states.

  18. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

  19. Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

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    Paola Fuentes-Claramonte

    Full Text Available Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

  20. Existence and control of Go/No-Go decision transition threshold in the striatum.

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    Jyotika Bahuguna

    2015-04-01

    Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

  1. Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder.

    Science.gov (United States)

    Cai, Chenxi; Yuan, Kai; Yin, Junsen; Feng, Dan; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Jin, Chenwang; Qin, Wei; Tian, Jie

    2016-03-01

    Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD.

  2. Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2004-01-01

    Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2→3.9%, CA: 57.4→14.1%, ST: 17.7→0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction

  3. Evidence that Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    OpenAIRE

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Logan, Jean; Benveniste, Helene; Kim, Ron; Thanos, Panayotis K.; Ferré, Sergi

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [11C]raclopride in controls) in striatum, but could not determine if this reflected dopamine increases ([11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases in...

  4. Distribution of GABAergic interneurons and dopaminergic cells in the functional territories of the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2012-01-01

    The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in

  5. Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats.

    Science.gov (United States)

    Ortiz-Pulido, R; Hernández-Briones, Z S; Tamariz-Rodríguez, A; Hernández, M E; Aranda-Abreu, G E; Coria-Avila, G A; Manzo, J; García, L I

    2017-06-01

    Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals.

    Science.gov (United States)

    Hwang, J W; Xin, S C; Ou, Y M; Zhang, W Y; Liang, Y L; Chen, J; Yang, X Q; Chen, X Y; Guo, T W; Yang, X J; Ma, W H; Li, J; Zhao, B C; Tu, Y; Kong, J

    2016-05-01

    Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

    Science.gov (United States)

    Xue, Bing; Chen, Elton C; He, Nan; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2017-01-01

    Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward.

    Science.gov (United States)

    Kishida, Kenneth T; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R; Laxton, Adrian W; Tatter, Stephen B; White, Jason P; Ellis, Thomas L; Phillips, Paul E M; Montague, P Read

    2016-01-05

    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson's disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson's disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.

  9. Characteristics of fast-spiking neurons in the striatum of behaving monkeys.

    Science.gov (United States)

    Yamada, Hiroshi; Inokawa, Hitoshi; Hori, Yukiko; Pan, Xiaochuan; Matsuzaki, Ryuichi; Nakamura, Kae; Samejima, Kazuyuki; Shidara, Munetaka; Kimura, Minoru; Sakagami, Masamichi; Minamimoto, Takafumi

    2016-04-01

    Inhibitory interneurons are the fundamental constituents of neural circuits that organize network outputs. The striatum as part of the basal ganglia is involved in reward-directed behaviors. However, the role of the inhibitory interneurons in this process remains unclear, especially in behaving monkeys. We recorded the striatal single neuron activity while monkeys performed reward-directed hand or eye movements. Presumed parvalbumin-containing GABAergic interneurons (fast-spiking neurons, FSNs) were identified based on narrow spike shapes in three independent experiments, though they were a small population (4.2%, 42/997). We found that FSNs are characterized by high-frequency and less-bursty discharges, which are distinct from the basic firing properties of the presumed projection neurons (phasically active neurons, PANs). Besides, the encoded information regarding actions and outcomes was similar between FSNs and PANs in terms of proportion of neurons, but the discharge selectivity was higher in PANs than that of FSNs. The coding of actions and outcomes in FSNs and PANs was consistently observed under various behavioral contexts in distinct parts of the striatum (caudate nucleus, putamen, and anterior striatum). Our results suggest that FSNs may enhance the discharge selectivity of postsynaptic output neurons (PANs) in encoding crucial variables for a reward-directed behavior. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

    Science.gov (United States)

    Kishida, Kenneth T.; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R.; Laxton, Adrian W.; Tatter, Stephen B.; White, Jason P.; Ellis, Thomas L.; Phillips, Paul E. M.; Montague, P. Read

    2016-01-01

    In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons. PMID:26598677

  11. Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

    Science.gov (United States)

    Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

    2016-01-01

    The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

  12. SSRI antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum

    Science.gov (United States)

    Van Waes, Vincent; Beverley, Joel; Marinelli, Michela; Steiner, Heinz

    2010-01-01

    The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs that use psychostimulant “cognitive enhancers”. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2–5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factors zif 268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction liability of methylphenidate. PMID:20704593

  13. Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum.

    Science.gov (United States)

    Van Waes, Vincent; Beverley, Joel; Marinelli, Michela; Steiner, Heinz

    2010-08-01

    The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs who use psychostimulant 'cognitive enhancers'. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2-5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factor genes zif268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction potential of methylphenidate.

  14. Re-thinking the role of the dorsal striatum in egocentric/response strategy

    Directory of Open Access Journals (Sweden)

    Fanny BOTREAU

    2010-02-01

    Full Text Available 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.

  15. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    International Nuclear Information System (INIS)

    Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

    2002-01-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  16. High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

    2002-04-01

    The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

  17. Decreased rates of terpene emissions in Ornithopus compressus L. and Trifolium striatum L. by ozone exposure and nitrogen fertilization.

    Science.gov (United States)

    Llusia, Joan; Bermejo-Bermejo, Victoria; Calvete-Sogo, Héctor; Peñuelas, Josep

    2014-11-01

    Increasing tropospheric ozone (O3) and nitrogen soil availability (N) are two of the main drivers of global change. They both may affect gas exchange, including plant emission of volatiles such as terpenes. We conducted an experiment using open-top chambers to analyze these possible effects on two leguminous species of Mediterranean pastures that are known to have different O3 sensitivity, Ornithopus compressus and Trifolium striatum. O3 exposure and N fertilization did not affect the photosynthetic rates of O. compressus and T. striatum, although O3 tended to induce an increase in the stomatal conductance of both species, especially T. striatum, the most sensitive species. O3 and N soil availability reduced the emission of terpenes in O. compressus and T. striatum. If these responses are confirmed as a general pattern, O3 could affect the competitiveness of these species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Conducta alimenticia, supervivencia y crecimiento de juveniles silvestres de Graus nigra Philippi, 1887 en cautiverio (Perciformes: Kyphosidae Feeding behavior, survival, and growth of wild Graus nigra Philippi, 1887 juveniles in captivity (Perciformes: Kyphosidae

    Directory of Open Access Journals (Sweden)

    Héctor Flores

    2011-11-01

    Full Text Available Se colectaron juveniles silvestres de Graus nigra, que fueron aclimatados durante 30 días en estanques con flujo de agua abierto y a temperatura ambiente, siendo alimentados con alimento formulado. Los peces fueron separados en seis grupos que se mantuvieron en experimentación por 196 días. La supervivencia promedio fue de 80%. El crecimiento en longitud total mostró un incremento promedio del 93,3% para los juveniles grandes (grupos 4, 5 y 6 y 125% para los pequeños (grupos 1, 2 y 3. El crecimiento en peso total mostró un incremento promedio de 434% para los peces grandes (grupos 4, 5 y 6 y de 707% para los pequeños (grupos 1, 2 y 3. Se concluyó que G. nigra toleró el cautiverio y el manejo, con una supervivencia relativamente alta, lo que hace de ella una especie atractiva para la acuicultura chilena.Wild juveniles of Graus nigra were collected and acclimated for 30 days in ponds with open-water flow and ambient temperature; the specimens were given a formulated feed. Fish individuals were separated into six groups that were studied for 196 days. The average survival was 80%. The total length increased an average of 93.3% for large individuals (groups 4, 5, 6 and 125% for small ones (groups 1, 2, 3. The total weight showed an average increase of 434% for large fishes (groups 4, 5, 6 and 707% for small ones (groups 1, 2, 3. Graus nigra was found to tolerate captivity and handling, with a relatively high survival rate, making it an attractive species for aquaculture in Chile.

  19. Multimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Linlin Cong

    Full Text Available The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD, has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam, a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii reduced transverse relaxation time (T2* of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v cerebral blood flow was not significantly affected, and vi reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD.

  20. A molecular approach towards the taxonomy of fresh water prawns Macrobrachium striatum and M. equidens (Decapoda, Palaemonidae) using mitochondrial markers.

    Science.gov (United States)

    Jose, Deepak; Nidhin, B; Anil Kumar, K P; Pradeep, P J; Harikrishnan, M

    2016-07-01

    Genus Macrobrachium includes freshwater prawns which inhabit most diverse habitats ranging from low saline areas to inland hill streams and impounded water bodies. Being morphologically conserved, this genus has been exposed to severe disputes related to their taxonomy, systematics and phylogeny. Macrobrachium striatum and M. equidens represent two morphologically related congeneric species within this genus. Earlier, M. striatum was considered as a striped form of M. equidens. Though these species are now well-described morphologically and differentiated into two species, no molecular level investigation has been carried out in support of their speciation. We report a study on M. striatum and M. equidens with emphasis to their molecular data through mitochondrial markers (16S ribosomal RNA and cytochrome oxidase subunit I). Results obtained from developed molecular markers of the two species revealed considerable genetic differentiation between them. Phylogram generated using Minimum evolution and Neighbour joining analyses differentiated M. striatum and M. equidens as two independent species. Genetic distance data showed high interspecific divergence (ranging from 3.9% to 17.0% for 16S rRNA sequences and 13.8% to 21.0% for COI sequences) between M. striatum and M. equidens confirming the findings of phylogram. Hence, it could be delineated that M. striatum and M. equidens represent two distinct species within genus Macrobrachium with emphasis to their morphology and genetics.

  1. The dynamics driving the invasion of Brassica nigra and Foeniculum vulgare in California : the interaction of competition, herbivory, and seed source

    OpenAIRE

    Hanna, Victoria Anderson

    2014-01-01

    Invasive species are highly detrimental to economies and to ecosystems. To counter the negative effects of invasive plant species, a better understanding of the mechanisms driving their dominance and success is necessary. The factors of competition, herbivory, and seed source were examined using two plant species invasive to California- Brassica nigra and Foeniculum vulgare. It was found that B. nigra is affected by each factor individually but not by any interactions between the factors. F. ...

  2. Controle de Qualidade e triagem fitoquímica da droga vegetal das folhas de Morus nigra L. (MORACEAE

    Directory of Open Access Journals (Sweden)

    Pedro Luis Guizzo

    2015-10-01

    Full Text Available Uma rigorosa análise de controle de qualidade é uma das etapas na produção de fitoterápicos. Devido a escassez de estudos sobre Morus nigra L. (MORACEAE, mais conhecida como amora, este trabalho teve como objetivo o controle de qualidade das folhas da amoreira, incluindo uma análise Fitoquímica preliminar, controle de qualidade físico-químico e microbiológico utilizando metodologias farmacopeicas e não farmacopeicas. Os testes fitoquímicos evidenciaram a presença de isoflavonas, taninos hidrolisáveis e alcaloides. Os resultados do controle físico-químico e microbiológico mostraram-se de acordo com as especificações. Isso destaca a importância do estabelecimento de normas para o controle da qualidade para as plantas, a fim de que sejam utilizadas como fitoterápicos.Palavras-chave: Controle de qualidade. Droga vegetal. Fitoquímica. Morus nigra. ABSTRACT A rigorous quality control analysis is one of the steps in the production of herbal medicines. Due to lack of studies on Morus nigra L. (Moraceae, better known as mulberry, this study had as objective the quality control of mulberry leaves, including a preliminary Phytochemical analysis of physical-chemical and microbiological quality control methodologies, using pharmacopoeic and non pharmacopoeic. Phytochemicals tests revealed the presence of isoflavones, hydrolysable tannins and alkaloids. The results of the physic-chemical and microbiological control shown in accordance with the specifications. This shows the importance of establishing standards for quality control for plants, to be used as herbal medicines.Keywords: Quality control. vegetal drug. Phytochemistry. Morus nigra.

  3. Wood identification of Dalbergia nigra (CITES Appendix I) using quantitative wood anatomy, principal components analysis and naïve Bayes classification

    Science.gov (United States)

    Gasson, Peter; Miller, Regis; Stekel, Dov J.; Whinder, Frances; Ziemińska, Kasia

    2010-01-01

    Background and Aims Dalbergia nigra is one of the most valuable timber species of its genus, having been traded for over 300 years. Due to over-exploitation it is facing extinction and trade has been banned under CITES Appendix I since 1992. Current methods, primarily comparative wood anatomy, are inadequate for conclusive species identification. This study aims to find a set of anatomical characters that distinguish the wood of D. nigra from other commercially important species of Dalbergia from Latin America. Methods Qualitative and quantitative wood anatomy, principal components analysis and naïve Bayes classification were conducted on 43 specimens of Dalbergia, eight D. nigra and 35 from six other Latin American species. Key Results Dalbergia cearensis and D. miscolobium can be distinguished from D. nigra on the basis of vessel frequency for the former, and ray frequency for the latter. Principal components analysis was unable to provide any further basis for separating the species. Naïve Bayes classification using the four characters: minimum vessel diameter; frequency of solitary vessels; mean ray width; and frequency of axially fused rays, classified all eight D. nigra correctly with no false negatives, but there was a false positive rate of 36·36 %. Conclusions Wood anatomy alone cannot distinguish D. nigra from all other commercially important Dalbergia species likely to be encountered by customs officials, but can be used to reduce the number of specimens that would need further study. PMID:19884155

  4. Fine-scale spatial genetic structure of Dalbergia nigra (Fabaceae), a threatened and endemic tree of the Brazilian Atlantic Forest.

    Science.gov (United States)

    de Oliveira Buzatti, Renata Santiago; Ribeiro, Renata Acácio; de Lemos Filho, José Pires; Lovato, Maria Bernadete

    2012-12-01

    The Atlantic Forest is one of the most diverse ecosystems in the world and considered a hotspot of biodiversity conservation. Dalbergia nigra (Fabaceae) is a tree endemic to the Brazilian Atlantic Forest, and has become threatened due to overexploitation of its valuable timber. In the present study, we analyzed the genetic diversity and fine-scale spatial genetic structure of D. nigra in an area of primary forest of a large reserve. All adult individuals (N = 112) were sampled in a 9.3 ha plot, and genotyped for microsatellite loci. Our results indicated high diversity with a mean of 8.6 alleles per locus, and expected heterozygosity equal to 0.74. The co-ancestry coefficients were significant for distances among trees up to 80 m. The Sp value was equal to 0.017 and indirect estimates of gene dispersal distances ranged from 89 to 144 m. No strong evidence of bottleneck or effects of human-disturbance was found. This study highlights that long-term efforts to protect a large area of Atlantic Forest have been effective towards maintaining the genetic diversity of D. nigra. The results of this study are important towards providing a guide for seed collection for ex-situ conservation and reforestation programmes of this threatened species.

  5. Effects of aging on nitrergic system in human basal nuclei

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    Bruno Lopes dos Santos

    2014-10-01

    Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

  6. Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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    Katsuo Kimura

    Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

  7. Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain.

    Science.gov (United States)

    Chen, Yishen; Derkach, Victor A; Smith, Peter A

    2016-05-01

    Synapses transmitting nociceptive information in the spinal dorsal horn undergo enduring changes following peripheral nerve injury. Indeed, such injury alters the expression of the GluA2 subunit of glutamatergic AMPA receptors (AMPARs) in the substantia gelatinosa and this predicts altered channel conductance and calcium permeability, leading to an altered function of excitatory synapses. We therefore investigated the functional properties of synaptic AMPA receptors in rat substantia gelatinosa neurons following 10-20d chronic constriction injury (CCI) of the sciatic nerve; a model of neuropathic pain. We measured their single-channel conductance and sensitivity to a blocker of calcium permeable AMPA receptors (CP-AMPARs), IEM1460 (50μM). In putative inhibitory, tonic firing neurons, CCI reduced the average single-channel conductance of synaptic AMPAR from 14.4±3.5pS (n=12) to 9.2±1.0pS (n=10, pinjury acting at synapses of inhibitory neurons to reduce their drive and therefore inhibitory tone in the spinal cord, therefore contributing to the central sensitization associated with neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Phenology of lilac (Syringa vulgaris) and elderberry (Sambucus nigra) as the indicator of spring warming

    Science.gov (United States)

    Vincze, E.; Hunkár, M.; Dunkel, Z.

    2012-04-01

    Phenological observations in Hungary started in 1871. The observation system collapsed and revived time by time. The aim of the observations as well as the locations, the methods and observed plants have been changed many times, therefore data series for a given plant species derived from the same place are rare. If we want to study the responses of biosphere to climate variability we need long time data series from the same places, especially phenological data of native plants. Phenological observations organized by the Hungarian Meteorological Service between 1983- 1999 contain valuable data for lilac (Syringa vulgaris) and elderberry (Sambucus nigra). Those perennial native plants are good indicators of spring warming therefore it is worth to study their phenological development concerning to climate variability. Eight locations in Hungary were selected where the site of the observations remaind the same year by year. Observed phenological phases were: Sprouting of leaves (SL, BBCH:11); Begin of Flowers (BF, BBCH:61); Fall of leaves (FO, BBCH:95). Spatial and temporal trends and variability of phenophases will be presented. The effect of meteorological conditions is studied to build up phenological model controlled by the temperature. Growing degree days above the base temperature was involved together with the duration and severeness of the chilling period. The study is supported by the National Scientific Foundation (OTKA-81979).

  9. Phytochemical Content of Some Black (Morus nigra L. and Purple (Morus rubra L. Mulberry Genotypes

    Directory of Open Access Journals (Sweden)

    Murat Tosun

    2010-01-01

    Full Text Available Bright black (Morus nigra and purple mulberry (Morus rubra are particularly desirable fruits in Turkey. More recently, the interest in these bright black and purple mulberry fruits has also increased because of the popularization of healthy properties of these fruits. The study was carried out in 2008 aiming to determine the antioxidant activity (ferric reducing ability of plasma, FRAP, total phenolic, total anthocyanin, mineral, soluble solid, vitamin C, and total acid content of four black and four purple mulberry genotypes grown in Turkey. The results show that black mulberry genotypes have a higher bioactive content than purple mulberry genotypes. The average total phenolic content and total anthocyanins of black mulberry genotypes were 2149 μg of gallic acid equivalent (GAE per g and 719 μg of cyanidin 3-glucoside equivalent (Cy 3-glu per g of fresh mass. In purple mulberry, these values were for GAE 1690 μg/g and for Cy 3-glu 109 μg/g on fresh mass basis. The average antioxidant activity of black mulberry genotypes was also found to be higher than that of the purple ones according to FRAP assay (Trolox equivalent (TE per fresh mass of black and purple mulberries was 13.35 and 6.87 μmol/g, respectively.

  10. ENRAIZAMENTO IN VITRO DE BROTOS DE JACARANDÁ-DA-BAHIA (DALBERGIA NIGRA VELLOZO

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    Aline Tintori Mantovani

    2017-02-01

    Full Text Available Resumo: A espécie Dalbergia nigra é conhecida popularmente como jacarandá-da-bahia. Devido ao seu destaque e importância econômica, a exploração para uso madeireiro e a pecuária acarretou devastação no seu ambiente natural o que a incluiu na lista de espécies da flora brasileira ameaçadas de extinção e apesar disso, pouco tem sido feito para a multiplicação desta espécie devido ao seu crescimento lento. A micropropagação é uma alternativa para obtenção de grande quantidade de mudas sadias em curto espaço de tempo. Objetivou-se neste estudo avaliar as condições mais favoráveis ao enraizamento de brotos in vitro, possibilitando a produção de plântulas viáveis. Foram utilizados meristemas apicais e cotiledonares de plântulas de jacarandá-da-bahia, cultivadas em condições assépticas nos tratamentos compostos por meio de cultura MS e concentrações de ANA (0 e 1 µM. O meio de cultura contendo 1 μM ANA após 30 dias de cultivo induziu a formação de raízes, apresentando melhores resultados.

  11. Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae

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    G. R. Souza

    2017-08-01

    Full Text Available Abstract This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH. The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH radical scavenging and β-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt. The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 μg/mL for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.

  12. A new antioxidant stilbene and other constituents from the stem bark of Morus nigra L.

    Science.gov (United States)

    Abbas, Ghada M; Abdel Bar, Fatma M; Baraka, Hany N; Gohar, Ahmed A; Lahloub, Mohammed-Farid

    2014-01-01

    A new stilbene, 2',3,4',5,5'-pentahydroxy-cis-stilbene (1), along with 13 known compounds, resveratrol (2), oxyresveratrol (3), norartocarpetin (4), kuwanon C (5), morusin (6), cudraflavone A (7), kuwanon G (8), albafurane C (9), mulberrofuran G (10), 3-O-acetyl-α-amyrin (11), 3-O-acetyl-β-amyrin (12) ursolic acid-3-O-acetate (13) and uvaol (14), were isolated from the barks of Morus nigra. Compounds 2, 8, 10, 12 and 14 are reported for the first time from this plant. The isolated compounds were elucidated by means of 1D and 2D NMR, UV, IR and MS, as well as by comparison with the literature data. The isolated compounds and the different extracts were evaluated for their potential antioxidant activity using 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)(+) radical-scavenging capacity assay and compared with ascorbic acid. The new stilbene (1) exhibited remarkable antioxidant capacity with IC50 of 4.69 μM.

  13. Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae).

    Science.gov (United States)

    Souza, G R; Oliveira-Junior, R G; Diniz, T C; Branco, A; Lima-Saraiva, S R G; Guimarães, A L; Oliveira, A P; Pacheco, A G M; Silva, M G; Moraes-Filho, M O; Costa, M P; Pessoa, C Ó; Almeida, J R G S

    2017-08-17

    This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 μg/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.

  14. Interactive effects of substrate, hydroperiod, and nutrients on seedling growth of Salix nigra and Taxodium distichum

    Science.gov (United States)

    Day, Richard H.; Doyle, T.W.; Draugelis-Dale, R. O.

    2006-01-01

    The large river swamps of Louisiana have complex topography and hydrology, characterized by black willow (Salix nigra) dominance on accreting alluvial sediments and vast areas of baldcypress (Taxodium distichum) deepwater swamps with highly organic substrates. Seedling survival of these two wetland tree species is influenced by their growth rate in relation to the height and duration of annual flooding in riverine environments. This study examines the interactive effects of substrate, hydroperiod, and nutrients on growth rates of black willow and baldcypress seedlings. In a greenhouse experiment with a split-split-plot design, 1-year seedlings of black willow and baldcypress were subjected to two nutrient treatments (unfertilized versus fertilized), two hydroperiods (continuously flooded versus twice daily flooding/draining), and two substrates (sand versus commercial peat mix). Response variables included height, diameter, lateral branch count, biomass, and root:stem ratio. Black willow growth in height and diameter, as well as all biomass components, were significantly greater in peat substrate than in sand. Black willow showed a significant hydroperiod-nutrient interaction wherein fertilizer increased stem and root biomass under drained conditions, but flooded plants did not respond to fertilization. Baldcypress diameter and root biomass were higher in peat than in sand, and the same two variables increased with fertilization in flooded as well as drained treatments. These results can be used in Louisiana wetland forest models as inputs of seedling growth and survival, regeneration potential, and biomass accumulation rates of black willow and baldcypress.

  15. Association genetics of chemical wood properties in black poplar (Populus nigra).

    Science.gov (United States)

    Guerra, Fernando P; Wegrzyn, Jill L; Sykes, Robert; Davis, Mark F; Stanton, Brian J; Neale, David B

    2013-01-01

    Black poplar (Populus nigra) is a potential feedstock for cellulosic ethanol production, although breeding for this specific end use is required. Our goal was to identify associations between single nucleotide polymorphism (SNP) markers within candidate genes encoding cellulose and lignin biosynthetic enzymes, with chemical wood property phenotypic traits, toward the aim of developing genomics-based breeding technologies for bioethanol production. Pyrolysis molecular beam mass spectrometry was used to determine contents of five- and six-carbon sugars, lignin, and syringyl : guaiacyl ratio. The association population included 599 clones from 17 half-sib families, which were successfully genotyped using 433 SNPs from 39 candidate genes. Statistical analyses were performed to estimate genetic parameters, linkage disequilibrium (LD), and single marker and haplotype-based associations. A moderate to high heritability was observed for all traits. The LD, across all candidate genes, showed a rapid decay with physical distance. Analysis of single marker-phenotype associations identified six significant marker-trait pairs, whereas nearly 280 haplotypes were associated with phenotypic traits, in both an individual and multiple trait-specific manner. The rapid decay of LD within candidate genes in this population and the genetic associations identified suggest a close relationship between the associated SNPs and the causative polymorphisms underlying the genetic variation of lignocellulosic traits in black poplar. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  16. Antimicrobial activity, phyto chemical profile and trace minerals of black mulberry (morus nigra l.) fresh juice

    International Nuclear Information System (INIS)

    Khalid, N.; Fawad, S.A.; Ahmed, I.

    2011-01-01

    In the present work, the fresh juice of black mulberry (Morus nigra) was tested for antimicrobial activity against various pathogenic microorganisms. Total antioxidant contents, total phenolic contents, total anthocyanins, trace minerals, total acid contents, total solids and ascorbic acid content were also evaluated. The results showed good antimicrobial activity both for Gram- positive and Gram-negative bacteria, with highest zones of inhibition for Bacillus spizizenii (19.68 mm, Gram-positive) and Pseudomonas aeruginosa (19.87 mm, Gram-negative). The black mulberry juice was rich in ascorbic acid (23.45 mg/100 g), had low overall acid content (1.60 %) and had 19% total soluble solids. The average total anthocyanins and total phenolic contents of black mulberry juice were 769 mu g/g of cyanidin 3-glucoside equivalent (Cy 3-gly) per gram and 2050 mu g of gallic acid equivalent (GAE) per gram of fresh juice. The average antioxidant activity (Trolox equivalent, TE) of fresh juice was 14.00 mu mol/g according to a FRAP assay and 20.10 mu mol/g according to a DPPH assay. The fresh juice was also rich in a variety of trace minerals. (author)

  17. Progressive supranuclear palsy: new concepts

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2010-12-01

    Full Text Available Progressive supranuclear palsy (PSP is a distinctive form of neurodegenerative disease which affects the brainstem and basal ganglia. Patients present supranuclear ophthalmoplegia, postural instability and mild dementia. PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus. Over the last decade many lines of investigations have helped refine PSP in many aspects and it is the purpose of this review to help neurologists identify PSP, to better understand its pathophysiology and to provide a more focused, symptom-based treatment approach.

  18. Cerebral glucose metabolism in Parkinson's disease

    International Nuclear Information System (INIS)

    Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

    1984-01-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  19. How compensation breaks down in Parkinson's disease

    DEFF Research Database (Denmark)

    Navntoft, Charlotte Amalie; Dreyer, Jakob Kisbye

    2016-01-01

    The bradykinesia and other motor signs of Parkinson's disease (PD) are linked to progressive loss of substantia nigra dopamine (DA) neurons innervating the striatum. However, the emergence of idiopathic PD is likely preceded by a prolonged subclinical phase, which may be masked by a variety of pre...... in the course of progressive nigrostriatal degeneration. In particular, we found that failure of DA signaling can occur by different mechanisms at different disease stages. We review these results and discuss their relevance for clinical and translational research, and we draw a number of predictions from our...

  20. Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

    International Nuclear Information System (INIS)

    Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

    2008-01-01

    Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

  1. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  2. Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

    Science.gov (United States)

    Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Mannisto, P. T.

    1992-01-01

    Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

  3. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  4. Monitoring extracellular pH, oxygen, and dopamine during reward delivery in the striatum of primates.

    Science.gov (United States)

    Ariansen, Jennifer L; Heien, Michael L A V; Hermans, Andre; Phillips, Paul E M; Hernadi, Istvan; Bermudez, Maria A; Schultz, Wolfram; Wightman, R Mark

    2012-01-01

    Dopamine projections that extend from the ventral tegmental area to the striatum have been implicated in the biological basis for behaviors associated with reward and addiction. Until recently, it has been difficult to evaluate the complex balance of energy utilization and neural activity in the striatum. Many techniques such as electrophysiology, functional magnetic resonance imaging (fMRI), and fast-scan cyclic voltammetry have been employed to monitor these neurochemical and neurophysiological changes. In this brain region, physiological responses to cues and rewards cause local, transient pH changes. Oxygen and pH are coupled in the brain through a complex system of blood flow and metabolism as a result of transient neural activity. Indeed, this balance is at the heart of imaging studies such as fMRI. To this end, we measured pH and O(2) changes with fast-scan cyclic voltammetry in the striatum as indices of changes in metabolism and blood flow in vivo in three Macaca mulatta monkeys during reward-based behaviors. Specifically, the animals were presented with Pavlovian conditioned cues that predicted different probabilities of liquid reward. They also received free reward without predictive cues. The primary detected change consisted of pH shifts in the striatal extracellular environment following the reward predicting cues or the free reward. We observed three types of cue responses that consisted of purely basic pH shifts, basic pH shifts followed by acidic pH shifts, and purely acidic pH shifts. These responses increased with reward probability, but were not significantly different from each other. The pH changes were accompanied by increases in extracellular O(2). The changes in pH and extracellular O(2) are consistent with current theories of metabolism and blood flow. However, they were of sufficient magnitude that they masked dopamine changes in the majority of cases. The findings suggest a role of these chemical responses in neuronal reward processing.

  5. Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum.

    Science.gov (United States)

    Hiroi, N; Graybiel, A M

    1996-10-07

    Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry. To explore the transcriptional events that might be involved in this neurochemical regulation, we used immunohistochemistry and immunoblotting to examine the expression patterns of two bZip transcription factors, c-Fos and FosB, in the striatum of rats treated acutely and chronically with neuroleptic drugs of different classes. Typical and atypical neuroleptic drugs produced contrasting regulatory effects on a FosB-like protein of ca. 36-39 kDa, the molecular weight of truncated FosB (delta FosB). Chronic treatments with two typical neuroleptics, haloperidol and metoclopramide, but not with the atypical neuroleptic clozapine, led to markedly enhanced FosB-like immunoreactivity in the caudoputamen. Further, c-Fos-like protein in the striatum, considered a marker for the induction of antipsychotic actions by neuroleptic treatments, was downregulated by chronic treatment with the two potent antipsychotic drugs tested, but not by chronic treatment with metoclopramide, which has low antipsychotic efficacy but induces extrapyramidal side effects. These results suggest that chronic treatments with neuroleptics having different effects on cognitive and motor behavior induce different long-term changes in transcription factor expression in the striatum. Nevertheless, we found that neuroleptics of both classes regulated transcription factor expression in overlapping populations of striatal neurons expressing enkephalin or DARPP-32. Contrasting patterns of transcriptional regulation in these neurons may thus contribute to the distinct neurochemical and behavioral effects that characterize neuroleptics of different classes.

  6. Differential effect of quetiapine and lithium on functional connectivity of the striatum in first episode mania.

    Science.gov (United States)

    Dandash, Orwa; Yücel, Murat; Daglas, Rothanthi; Pantelis, Christos; McGorry, Patrick; Berk, Michael; Fornito, Alex

    2018-03-06

    Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au.

  7. Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S; Logan, Jean; Benveniste, Helene; Kim, Ron; Thanos, Panayotis K; Ferré, Sergi

    2012-05-09

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [(11)C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([(11)C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [(11)C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  8. Functional interactions between dentate gyrus, striatum and anterior thalamic nuclei on spatial memory retrieval.

    Science.gov (United States)

    Méndez-Couz, M; Conejo, N M; González-Pardo, H; Arias, J L

    2015-04-24

    The standard model of memory system consolidation supports the temporal reorganization of brain circuits underlying long-term memory storage, including interactions between the dorsal hippocampus and extra-hippocampal structures. In addition, several brain regions have been suggested to be involved in the retrieval of spatial memory. In particular, several authors reported a possible role of the ventral portion of the hippocampus together with the thalamus or the striatum in the persistence of this type of memory. Accordingly, the present study aimed to evaluate the contribution of different cortical and subcortical brain regions, and neural networks involved in spatial memory retrieval. For this purpose, we used cytochrome c oxidase quantitative histochemistry as a reliable method to measure brain oxidative metabolism. Animals were trained in a hidden platform task and tested for memory retention immediately after the last training session; one week after completing the task, they were also tested in a memory retrieval probe. Results showed that retrieval of the previously learned task was associated with increased levels of oxidative metabolism in the prefrontal cortex, the dorsal and ventral striatum, the anterodorsal thalamic nucleus and the dentate gyrus of the dorsal and ventral hippocampus. The analysis of functional interactions between brain regions suggest that the dorsal and ventral dentate gyrus could be involved in spatial memory retrieval. In addition, the results highlight the key role of the extended hippocampal system, thalamus and striatum in this process. Our study agrees with previous ones reporting interactions between the dorsal hippocampus and the prefrontal cortex during spatial memory retrieval. Furthermore, novel activation patterns of brain networks involving the aforementioned regions were found. These functional brain networks could underlie spatial memory retrieval evaluated in the Morris water maze task. Copyright © 2015 Elsevier B

  9. Morphological features of neurons containing calcium-binding proteins in the human striatum.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A

    1998-01-26

    An immunohistochemical approach was used to characterize the morphological phenotype of neurons containing the calcium-binding proteins calretinin (CR), parvalbumin (PV), or calbindin-D28k (CB) in the normal human striatum. The protein CR occurs in at least four morphologically distinct types of neurons. Apart from the numerous medium-sized aspiny interneurons and the less abundant giant aspiny interneurons, CR also labels some medium-sized spiny neurons morphologically identical to striatal projection neurons. This finding indicates that CR is not only confined to striatal interneurons but also may be involved in the function of certain projection neurons. Some small and peculiar bushy-like aspiny neurons also are enriched with CR. These neurons could correspond to the dwarf or neurogliform neurons first described by Ramón y Cajal (1911). Three types of PV-immunoreactive striatal neurons can be visualized in the human striatum: 1) the common medium-sized aspiny leptodendritic neurons, 2) some smaller and profusely arborized aspiny neurons, and 3) a few large and intensely stained neurons with conspicuously beaded and poorly branched dendrites. The protein CB labels virtually all medium-sized spiny projection neurons located in the striatal matrix but also identifies a small subset of large and more intensely immunostained aspiny neurons. The latter finding indicates that CB is not entirely confined to striatal projection neurons but also may play a role in local circuit neurons. These normative data should help our understanding of the chemical anatomy of the human striatum in both health and disease.

  10. Chemical anatomy of the human ventral striatum and adjacent basal forebrain structures.

    Science.gov (United States)

    Prensa, Lucía; Richard, Sandra; Parent, André

    2003-06-02

    Calbindin D-28k (CB), calretinin (CR), substance P (SP), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) were used as chemical markers to investigate the organization of the ventral striatum (VST) and adjacent structures in healthy human individuals. No clear boundary could be established between the dorsal striatum and the VST, and the core/shell subdivisions of nucleus accumbens (Acb) could be distinguished only at the midrostrocaudal level of the VST. The CB-poor shell displayed intense immunostaining for SP and CR but only weak staining for LAMP. By contrast, the core was weakly stained for SP and CR and moderately stained for LAMP and CB. There was no difference between shell and core with regard to the cholinergic markers. The Acb harbored numerous ChAT- and CR-immunoreactive cell bodies, the latter being distributed according to a marked, mediolaterally increasing gradient. The size of the ChAT- and CR-immunoreactive perikarya in the Acb varied according to their location in the core and shell. The VST was surrounded by a chemically heterogeneous group of cell clusters referred to as interface islands. The CR-rich caudal portion of the VST merged with the bed nucleus of the stria terminalis dorsally and the diagonal band of Broca ventromedially, the latter two structures displaying complex immunostaining patterns. The claustrum was markedly enriched in LAMP and harbored different types of CR- and CB-immunopositive neurons. These results demonstrate that the neurochemical organization of the human VST is strikingly complex and exhibits a greater heterogeneity than the dorsal striatum. Copyright 2003 Wiley-Liss, Inc.

  11. Caffeine stimulates cytochrome oxidase expression and activity in the striatum in a sexually dimorphic manner.

    Science.gov (United States)

    Jones, Frederick S; Jing, Jie; Stonehouse, Anthony H; Stevens, Anthony; Edelman, Gerald M

    2008-09-01

    Epidemiological studies indicate that caffeine consumption reduces the risk of Parkinson's disease (PD) in men, and antagonists of the adenosine 2A receptor ameliorate the motor symptoms of PD. These findings motivated us to identify proteins whose expression is regulated by caffeine in a sexually dimorphic manner. Using mass spectroscopy, we found that Cox7c, a nuclear-encoded subunit of the mitochondrial enzyme cytochrome oxidase, is up-regulated in the striatum of male but not female mice after receiving a single dose of caffeine. The expression of two other Cox subunits, Cox1 and Cox4, was also stimulated by caffeine in a male-specific fashion. This up-regulation of Cox subunits by caffeine was accompanied by an increase in Cox enzyme activity in the male striatum. Caffeine-induced stimulation of Cox expression and activity were reproduced using the adenosine 2A receptor (A2AR)-specific antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-epsilon]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261), and coadministration of the A2AR-specific agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) counteracted the elevation of Cox expression and activity by caffeine. Caffeine also increased Cox activity in PC-12 cells. In contrast, small interfering RNA (siRNA) knockdown of Cox7c expression in PC-12 cells blunted Cox activity, and this was counteracted by caffeine treatment. Caffeine was also found to increase Cox7c mRNA expression in the striatum and in PC-12 cells. This occurred at the level of transcription and was mediated by a segment of the Cox7c promoter. Overall, these findings indicate that cytochrome oxidase is a metabolic target of caffeine and that stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in PD.

  12. Separate populations of neurons in ventral striatum encode value and motivation.

    Science.gov (United States)

    Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

    2013-01-01

    Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

  13. Identification of Functional Clusters in the Striatum Using Infinite Relational Modeling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Madsen, Kristoffer Hougaard; Siebner, Hartwig

    2011-01-01

    In this paper we investigate how the Infinite Relational Model can be used to infer functional groupings of the human striatum using resting state fMRI data from 30 healthy subjects. The Infinite Relational Model is a non-parametric Bayesian method for infering community structure in complex...... are involved in the same neural computations. The reproducibility of the groupings found are assessed by calculating mutual information between half splits of the subject sample for various hyperparameter values. Finally, the model's ability to predict unobserved links is assessed by randomly treating links...

  14. Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking

    DEFF Research Database (Denmark)

    Gjedde, Albert; Kumakura, Yoshitaka; Cumming, Paul

    2010-01-01

    Sensation seeking is a core personality trait that declines with age in both men and women, as do also both density and availability of the dopamine D(2/3) receptors in striatum and cortical regions. In contrast, novelty seeking at a given age relates inversely to dopamine receptor availability...... to dopamine concentrations. Higher dopamine occupancy and dopamine concentrations explain the motivation that drives afflicted individuals to seek sensations, in agreement with reduced protection against addictive behavior that is characteristic of individuals with low binding potentials....

  15. Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

    Science.gov (United States)

    Mattfeld, Aaron T.; Stark, Craig E. L.

    2015-01-01

    The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

  16. Morphological, biochemical and sensory characteristics of black mulberry fruits (Morus nigra L.

    Directory of Open Access Journals (Sweden)

    Beáta Stehlíková

    2013-02-01

    Full Text Available This work aimed at the morphological, biochemical, technological and sensorial determination of black mulberry (Morus nigra L. – MN  fruitage and their utilization in the food production branches. For the experimental purposes were selected 50 genotypes of this population grown in the Pukanec surroundings. The medium fruitage weight determined in the selected collection ranged from 7.26 g (MN-1 to 1.42 g (MN-14, fruitage length in a range of 13.51 mm (MN-14 to 29.20 mm (MN-12 and the medium fruitage width  11.88 mm (MN-14 – 21.12 mm (MN-2. The variability of the evaluated traits varried from low to high degree. Juice yield from matured fruitage achieved 62.40 %. From black mulberry fruitages 16 food products were prepared – juice mixed with cream, yoghurt and/or curd (in several proportions and 3 confectionery products. Sensorial analyses showed significant differences among tested products. In the group of confectionery products was generally preferred the cream-mulberry cake. High values of antioxidative activity has been measured in the chocolate cake with a mulberry jam (36.90 – 28.43 %, followed by the cream-mulberry cake (29.78 – 12.71 % and the fresh mulberry juice (30.97 – 20.17 %. The antioxidation activities exerted generally higher values with the samples tested in water, when compared with those prepared in ethanol extract. Based on the gained results 4 genotypes were selected and recommended for the use in practice, as these provided relative high values of tested traits.doi:10.5219/234

  17. Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner.

    Science.gov (United States)

    Ketzef, Maya; Spigolon, Giada; Johansson, Yvonne; Bonito-Oliva, Alessandra; Fisone, Gilberto; Silberberg, Gilad

    2017-05-17

    Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure

    Science.gov (United States)

    Kim, Hak Rim

    2016-01-01

    The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs). EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF) of 835 MHz at a specific absorption rate (SAR) of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress. PMID:27073885

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  1. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum

    Science.gov (United States)

    Goitia, Belen; Garcia-Rill, Edgar; Krasnova, Irina N.; Cadet, Jean Lud; Urbano, Francisco J.; Bisagno, Veronica

    2012-01-01

    Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. PMID:23056363

  2. The role of the dorsal striatum in extinction: A memory systems perspective.

    Science.gov (United States)

    Goodman, Jarid; Packard, Mark G

    2018-04-01

    The present review describes a role for the dorsal striatum in extinction. Evidence from brain lesion and pharmacological studies indicate that the dorsolateral region of the striatum (DLS) mediates extinction in various maze learning and instrumental learning tasks. Within the context of a multiple memory systems view, the role of the DLS in extinction appears to be selective. Specifically, the DLS mediates extinction of habit memory and is not required for extinction of cognitive memory. Thus, extinction mechanisms mediated by the DLS may involve response-produced inhibition (e.g. inhibition of existing stimulus-response associations or formation of new inhibitory stimulus-response associations), as opposed to cognitive mechanisms (e.g. changes in expectation). Evidence also suggests that NMDA-dependent forms of synaptic plasticity may be part of the mechanism through which the DLS mediates extinction of habit memory. In addition, in some learning situations, DLS inactivation enhances extinction, suggesting a competitive interaction between multiple memory systems during extinction training. Consistent with a multiple memory systems perspective, it is suggested that the DLS represents one of several distinct neural systems that specialize in extinction of different kinds of memory. The relevance of these findings to the development of behavioral and pharmacological therapies that target the maladaptive habit-like symptoms in human psychopathology is also briefly considered. Published by Elsevier Inc.

  3. Volumetry of striatum and pallidum in man--anatomy, cytoarchitecture, connections, MRI and aging.

    Science.gov (United States)

    Brabec, J; Krásený, J; Petrovický, P

    2003-01-01

    For comparing of the pathological and normal healthy state it is essential to obtain sufficient amount of the volumetric data. Nevertheless most of the publicized works use only few healthy controls opposite to the patients for the measuring of the basal ganglia volume. Further essential condition is to take into account the effect of age to the basal ganglia volume in such analysis. The goal of our study was (1) to give the current review of the structure, neurotransmitters, connections and general integration of the basal ganglia in the pathways of the central nervous system, (2) aggregate sufficient amount of volumetric data by virtue of MRI and post-mortem studies, and appoint volumes of the striatum and pallidum, (3) evaluate aging of these structures in adult healthy patients. Another goal was (4) to inspect the correlations between the size of the basal ganglia and volume characteristics of the brain, cranial capacity or frequently measured dimensions within CNS. In the spite of the fact that it is not possible to measure all of these dimensions for clinicians who want to determine if the structure is "normal" or not. Another goal was (5) to find a simple measure, which could serve as the indicator of the real size of structure of the interest. By virtue of the classical anatomical methods and MRI examination we appointed volumes of the striatum (furthermore divided into the complex of the caudatum--nucleus accumbens--CD-Acc and putamen) and pallidum in the sample of 108 healthy adults (18-89 years old). From another measurements we calculated the cranial capacity and volume characteristics of each brain. In a general view that does not respect changes due to age neither volumetric difference between two sexes nor interhemispheric difference was significant for absolute volumes of the striatum, CD-Acc complex, putamen and pallidum. In the case of the striatum, significant correlation between size and age was found (p complex CD-Acc (p = 0.061). Age related

  4. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2017-05-01

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

  5. In vivo [11C]dihydrotetrabenazine binding in rat striatum: sensitivity to dopamine concentrations

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.; Butch, Elizabeth R.; Desmond, Timothy; Sherman, Phillip; Harris, Paul E.; Frey, Kirk A.

    2010-01-01

    Introduction: The sensitivity of the in vivo binding of [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) and [ 11 C]methylphenidate ([ 11 C]MPH) to their respective targets - vesicular monoamine transporter type 2 (VMAT2) and neuronal membrane dopamine transporter - after alterations in endogenous levels of dopamine was examined in the rat brain. Methods: In vivo binding of [ 11 C]DTBZ and [ 11 C]MPH was determined using a bolus+infusion protocol. The in vitro number of VMAT2 binding sites was determined by autoradiography. Results: Repeated dosing with α-methyl-p-tyrosine (AMPT) at doses that significantly (-75%) depleted brain tissue dopamine levels resulted in increased (+36%) in vivo [ 11 C]DTBZ binding to VMAT2 in the striatum. The increase in binding could be completely reversed via treatment with L-DOPA/benserazide to restore dopamine levels. There were no changes in the total number of VMAT2 binding sites, as measured using in vitro autoradiography. No changes were observed for in vivo [ 11 C]MPH binding to the dopamine transporter in the striatum following AMPT pretreatment. Conclusion: These results indicate that large reductions in dopamine concentrations in the rat brain can produce modest but significant changes in the binding of radioligands to VMAT2, which can be reversed by replenishment of dopamine using exogenous L-DOPA.

  6. Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and Primate Striatum Activity

    Directory of Open Access Journals (Sweden)

    Ioan eOpris

    2011-05-01

    Full Text Available Although reward probability is an important factor that shapes animal behavior, it is not well understood however, how the primate brain translates reward expectation into the vigor of movement (reaction time and speed. To address this question, we trained two monkeys in a reaction time task that required wrist movements in response to vibrotactile and visual stimuli, with a variable reward schedule. Correct performance was rewarded in 75 % of the trials. Monkeys were certain that they would be rewarded only in the trials immediately following withheld rewards. In these trials, the animals responded sooner and moved faster. Single-unit recordings from the dorsal striatum revealed that modulations in striatal neurons reflected such modulations of movement vigor. First, in the trials with certain rewards, striatal neurons modulated their firing rates earlier. Second, magnitudes of changes in neuronal firing rates depended on whether or not monkeys were certain about the reward. Third, these modulations depended on the sensory modality of the cue (visual vs. vibratory and/or movement direction (flexions vs. extensions. We conclude that dorsal striatum may be a part of the mechanism responsible for the modulation of movement vigor in response to changes of reward predictability.

  7. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  8. Individual differences in striatum activity to food commercials predict weight gain in adolescents.

    Science.gov (United States)

    Yokum, Sonja; Gearhardt, Ashley N; Harris, Jennifer L; Brownell, Kelly D; Stice, Eric

    2014-12-01

    Adolescents view thousands of food commercials annually, but little is known about how individual differences in neural response to food commercials relate to weight gain. To add to our understanding of individual risk factors for unhealthy weight gain and environmental contributions to the obesity epidemic, we tested the associations between reward region (striatum and orbitofrontal cortex [OFC]) responsivity to food commercials and future change in body mass index (BMI). Adolescents (N = 30) underwent a scan session at baseline while watching a television show edited to include 20 food commercials and 20 nonfood commercials. BMI was measured at baseline and 1-year follow-up. Activation in the striatum, but not OFC, in response to food commercials relative to nonfood commercials and in response to food commercials relative to the television show was positively associated with change in BMI over 1-year follow-up. Baseline BMI did not moderate these effects. The results suggest that there are individual differences in neural susceptibility to food advertising. These findings highlight a potential mechanism for the impact of food marketing on adolescent obesity. © 2014 The Obesity Society.

  9. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments

    International Nuclear Information System (INIS)

    Graybiel, A.M.; Moratalla, R.

    1989-01-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses in reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. The authors have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. The authors report here that desipramine-sensitive [ 3 H]mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, [ 3 H]mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, and that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP + ), that depend on the dopamine-uptake complex for entry into neurons

  10. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments.

    Science.gov (United States)

    Graybiel, A M; Moratalla, R

    1989-01-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses is reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. We have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. We report here that desipramine-sensitive [3H]mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, [3H]mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP+), that depend on the dopamine-uptake complex for entry into neurons. Images PMID:2813436

  11. Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum.

    Science.gov (United States)

    Zimányi, I; Lajtha, A; Reith, M E

    1989-12-01

    Biochemical and pharmacological studies suggest that the binding of [3H]mazindol is functionally related to the dopamine uptake carrier complex in rodent striatum. In order to study further the relationship between the substrate recognition site for dopamine uptake and the high-affinity binding site for mazindol the uptake of [3H]dopamine and the binding of [3H]mazindol was studied in BALB/cBy mouse striatum in various buffers (Tris, HEPES, bicarbonate-phosphate). Kinetic analysis showed that the Kd of the binding of [3H]mazindol and the Km of the uptake of [3H]dopamine was changed by different sodium concentrations and/or by the presence of Tris, while the Bmax and the Vmax remained essentially the same. However, the shape of the Na+ dependency curves was not the same for mazindol binding and dopamine uptake in the various buffers. The inhibitory effect of other cations such as K+ and Tris was also different on binding and uptake under similar experimental circumstances. Dopamine did not slow down the dissociation of mazindol from its site and this effect was not sodium-sensitive. These complexities can be accommodated by a model that involves overlapping sites for mazindol and dopamine on the dopamine uptake carrier complex, and translocation-reorientation steps.

  12. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments

    Energy Technology Data Exchange (ETDEWEB)

    Graybiel, A.M.; Moratalla, R. (Massachusetts Institute of Technology, Cambridge (USA))

    1989-11-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses in reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. The authors have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. The authors report here that desipramine-sensitive ({sup 3}H)mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, ({sup 3}H)mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, and that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP{sup +}), that depend on the dopamine-uptake complex for entry into neurons.

  13. Neuronal Adaptation to Amphetamine and Dopamine: Molecular Mechanisms of Prodynorphin Gene Regulation in Rat Striatum

    Science.gov (United States)

    Cole, Rebecca L.; Konradi, Christine; Douglass, James; Hyman, Steven E.

    2014-01-01

    Summary Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, levels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum. PMID:7718243

  14. Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

    International Nuclear Information System (INIS)

    Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

    2013-01-01

    In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

  15. Vanadium K-edge x-ray absorption spectroscopy reveals species differences within the same ascidian genera. A comparison of whole blood from Ascidia nigra and Ascidia ceratodes.

    Science.gov (United States)

    Frank, P; Hodgson, K O; Kustin, K; Robinson, W E

    1998-09-18

    Vanadium K-edge x-ray absorption spectroscopy (XAS) was used to examine whole blood preparations from the tunicates Ascidia nigra and Ascidia ceratodes. Each XAS spectrum exhibits a rising edge inflection near 5480 eV characteristic of vanadium(III) and an intensity maximum at 5484.0 eV. In A. ceratodes blood cells, intrinsic aquo-VSO4+ complex ion is indicated by an inflection feature at 5476 eV in the first derivative of the vanadium K-edge XAS spectrum, but this feature is notably absent from the first derivative of the vanadium K-edge spectrum of blood cells from A. nigra. A strong pre-edge feature at 5468.6 eV also uniquely distinguishes the vanadium K-edge XAS spectrum of A. nigra blood cells, implying that vanadyl ion represents approximately 25% of the endogenous vanadium. However, the energy position of the rising edge inflection of the vanadium K-edge XAS spectrum of A. nigra (5479.5 eV) is 1 eV lower than that of A. ceratodes (5480.5 eV), the reverse of any expected shift arising from the endogenous vanadyl ion. Thus, in contrast to A. ceratodes, a significant fraction of the blood cell vanadium(III) in A. nigra is apparently in a ligation environment substantially different from that provided by water. These novel species-related differences may have taxonomic significance.

  16. Extracts of Morus nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity

    Science.gov (United States)

    Fontes, Pedro Ribeiro; Souza, Paula Monteiro; William Fagg, Christopher; Neves Silva Guerra, Eliete; de Medeiros Nóbrega, Yanna Karla; Silveira, Damaris; Fonseca-Bazzo, Yris; Simeoni, Luiz Alberto; Homem-de-Mello, Maurício; Oliveira Magalhães, Pérola

    2016-01-01

    Melanogenesis is a process responsible for melanin production, which is stored in melanocytes containing tyrosinase. Inhibition of this enzyme is a target in the cosmetics industry, since it controls undesirable skin conditions such as hyperpigmentation due to the overproduction of melanin. Species of the Morus genus are known for the beneficial uses offered in different parts of its plants, including tyrosinase inhibition. Thus, this project aimed to study the inhibitory activity of tyrosinase by extracts from Morus nigra leaves as well as the characterization of its chromatographic profile and cytotoxicity in order to become a new therapeutic option from a natural source. M. nigra leaves were collected, pulverized, equally divided into five batches and the standardized extract was obtained by passive maceration. There was no significant difference between batches for total solids content, yield and moisture content, which shows good reproducibility of the extraction process. Tyrosinase enzymatic activity was determined for each batch, providing the percentage of enzyme inhibition and IC50 values obtained by constructing dose-response curves and compared to kojic acid, a well-known tyrosinase inhibitor. High inhibition of tyrosinase activity was observed (above 90% at 15.625 μg/mL). The obtained IC50 values ranged from 5.00 μg/mL ± 0.23 to 8.49 μg/mL ± 0.59 and were compared to kojic acid (3.37 μg/mL ± 0.65). High Performance Liquid Chromatography analysis revealed the presence of chlorogenic acid, rutin and, its major compound, isoquercitrin. The chromatographic method employed was validated according to ICH guidelines and the extract was standardized using these polyphenols as markers. Cytotoxicity, assessed by MTT assay, was not observed on murine melanomas, human keratinocytes and mouse fibroblasts in tyrosinase IC50 values. This study demonstrated the potential of M. nigra leaf extract as a promising whitening agent of natural source against skin

  17. Identification of black pine (Pinus nigra Arn.) heartwood as a rich source of bioactive stilbenes by qNMR.

    Science.gov (United States)

    Ioannidis, Kostas; Melliou, Eleni; Alizoti, Paraskevi; Magiatis, Prokopios

    2017-04-01

    Recently published studies have demonstrated the strong anti-inflammatory properties of Scots pine (Pinus sylvestris L.) heartwood extracts, related to its stilbene content. In order to find alternative sources of Pinus heartwood extracts rich in stilbenes, a large number of samples were investigated, using a new developed high-throughput screening method based on quantitative nuclear magnetic resonance. The new method enabled us to measure the levels of pinosylvin, pinosylvin monomethyl ether and pinosylvin dimethyl ether in heartwood extracts in only 45 s per sample. The method was applied to 260 Pinus nigra trees originating from Peloponnese (southern Greece) from four different natural populations of the species. The results obtained showed that the total stilbenoids per dry heartwood weight varied greatly, ranging from 10.9 to 128.2 mg g -1 drywood (average 59.92 ± 21.79 mg g -1 drywood ). The major stilbene in all cases was pinosylvin monomethyl ether (40.32 ± 15.55 mg g -1 drywood ), followed by pinosylvin (17.07±6.76 mg g -1 drywood ) and pinosylvin dimethyl ether (2.54 ± 1.22 mg g -1 drywood ). The highest stilbene content of P. nigra samples was found to be 6.3 times higher than the highest reported figure for P. sylvestris L. Pinus nigra heartwood is the richest source of pinosylvin and pinosylvin monomethyl ether identified to date and can be considered the best natural resource for production of bioactive extracts. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Future scenarios and conservation strategies for a rear-edge marginal population of Pinus nigra Arnold in Italian central Apennines

    Energy Technology Data Exchange (ETDEWEB)

    Marchi, M.; Nocentini, S.; Ducci, F.

    2016-07-01

    Aim of the study: To forecast the effects of climate change on the spatial distribution of Black pine of Villetta Barrea in its natural range and to define a possible conservation strategy for the species. Area of study: A rear-edge marginal population of Pinus nigra spp. nigra in Abruzzo region, central Italian Apennines. Matherials and Methods: For its adaptive and genetic traits this population is considered endemic of the Italian peninsula and represents a rear-edge marginal population of nigra subspecies. The spatial distribution of the tree in the administrative Region (Abruzzo) was used to define the ecological traits while three modelling techniques (GLM, GAM, Random Forest) were used to build a Species distribution model according to two climatic scenarios. Main results: The marginal population's range was predicted to shift at higher elevations as consequence of climatic adaptation. Many zones, represented by the higher part of the mountains surrounding the study area (currently bare and inhospitable for trees), were identified as suitable in future for the species. However, in the case of a rapid climate change, this marginal population may not be able to move as fast as necessary. An in-situ adaptive management integrated with an assisted migration protocol might be considered to enforce the natural regeneration and improve the richness and variability of the genetic pool. Research highlights: Most of the genetic richness is held in small populations at the borders of natural distribution of forest species. Monitoring this MAP could be useful to understand the adaptive processes of the species and could support the future management of many other within-core populations. (Author)

  19. Extracts of Morus nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Marcela Medeiros de Freitas

    Full Text Available Melanogenesis is a process responsible for melanin production, which is stored in melanocytes containing tyrosinase. Inhibition of this enzyme is a target in the cosmetics industry, since it controls undesirable skin conditions such as hyperpigmentation due to the overproduction of melanin. Species of the Morus genus are known for the beneficial uses offered in different parts of its plants, including tyrosinase inhibition. Thus, this project aimed to study the inhibitory activity of tyrosinase by extracts from Morus nigra leaves as well as the characterization of its chromatographic profile and cytotoxicity in order to become a new therapeutic option from a natural source. M. nigra leaves were collected, pulverized, equally divided into five batches and the standardized extract was obtained by passive maceration. There was no significant difference between batches for total solids content, yield and moisture content, which shows good reproducibility of the extraction process. Tyrosinase enzymatic activity was determined for each batch, providing the percentage of enzyme inhibition and IC50 values obtained by constructing dose-response curves and compared to kojic acid, a well-known tyrosinase inhibitor. High inhibition of tyrosinase activity was observed (above 90% at 15.625 μg/mL. The obtained IC50 values ranged from 5.00 μg/mL ± 0.23 to 8.49 μg/mL ± 0.59 and were compared to kojic acid (3.37 μg/mL ± 0.65. High Performance Liquid Chromatography analysis revealed the presence of chlorogenic acid, rutin and, its major compound, isoquercitrin. The chromatographic method employed was validated according to ICH guidelines and the extract was standardized using these polyphenols as markers. Cytotoxicity, assessed by MTT assay, was not observed on murine melanomas, human keratinocytes and mouse fibroblasts in tyrosinase IC50 values. This study demonstrated the potential of M. nigra leaf extract as a promising whitening agent of natural source

  20. Antioxidant responses and photosynthetic behaviors of Kappaphycus alvarezii and Kappaphycus striatum (Rhodophyta, Solieriaceae) during low temperature stress.

    Science.gov (United States)

    Li, Hu; Liu, Jianguo; Zhang, Litao; Pang, Tong

    2016-12-01

    Kappaphycus are farmed in tropical countries as raw material for carrageenan, which is widely used in food industry. The sea area available for farming is one limiting factor in the production of seaweeds. Though cultivation is spreading into subtropical regions, the lower seawater temperature is an important problem encountered in subtropical regions for the farming of Kappaphycus. This research of physiological response to low temperature stress will be helpful for screening Kappaphycus strains for growth in a lower temperature environment. Responses of antioxidant systems and photosystem II (PSII) behaviors in Kappaphycus alvarezii and Kappaphycus striatum were evaluated during low temperature treatments (23, 20, 17 °C). Compared with the controls at 26 °C, the H 2 O 2 concentrations increased in both species when the thalli were exposed to low temperatures (23, 20, 17 °C), but these increases were much greater in K. striatum than in K. alvarezii thalli, suggesting that K. striatum suffered more oxidative stress. The activities of some important antioxidant enzymes (e.g. superoxide dismutase and ascorbate peroxidase) and the hydroxyl free radical scavenging capacity were substantially higher at 23, 20 and 17 °C than at the control 26 °C in K. alvarezii, indicating that the antioxidant system of K. alvarezii enhanced its resistance to low temperature. However, no significant increases of antioxidant enzymes activities were observed at 20 and 17 °C in K. striatum. In addition, both the maximal efficiency of PSII photochemistry (F V /F m ) and the performance index (PI ABS ) decreased significantly in K. striatum at 23 °C, indicating that the photosynthetic apparatus was damaged at 23 °C. In contrast, no significant decreases of either F V /F m or PI ABS were observed in K. alvarezii at 23 °C. It is concluded that K. alvarezii has greater tolerance to low temperature than K. striatum.

  1. Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

    Directory of Open Access Journals (Sweden)

    Julie eBoulanger Bertolus

    2014-05-01

    Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

  2. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  3. Controle de Qualidade e triagem fitoquímica da droga vegetal das folhas de Morus nigra L. (MORACEAE)

    OpenAIRE

    Pedro Luis Guizzo; Thaís Cristina Cuba Bredda; Maria Virgínia Costa Scarpa; Fernanda Flores Navarro

    2015-01-01

    Uma rigorosa análise de controle de qualidade é uma das etapas na produção de fitoterápicos. Devido a escassez de estudos sobre Morus nigra L. (MORACEAE), mais conhecida como amora, este trabalho teve como objetivo o controle de qualidade das folhas da amoreira, incluindo uma análise Fitoquímica preliminar, controle de qualidade físico-químico e microbiológico utilizando metodologias farmacopeicas e não farmacopeicas. Os testes fitoquímicos evidenciaram a presença de isoflavonas, taninos hidr...

  4. Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

    DEFF Research Database (Denmark)

    Peterson, Ericka; Gjedde, Albert; Møller, Arne

    Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs...... of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare striatal pB data obtained using three routine analyses of raclopride data...

  5. Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

    DEFF Research Database (Denmark)

    Peterson, Ericka; Gjedde, Albert; Møller, Arne

    Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing  effects of virtually all drugs...... of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride  as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare  striatal pB data obtained using three routine analyses of raclopride data...

  6. Impact mortality of black storks (Ciconia nigra) on medium-voltage overhead power lines in Rheinland-Pfalz; Anflugverluste von Schwarzstoerchen (Ciconia nigra) an Mittelspannungsfreileitungen in Rheinland-Pfalz

    Energy Technology Data Exchange (ETDEWEB)

    Hormann, M.; Richarz, K. [Staatliche Vogelschutzwarte fuer Hessen, Rheinland-Pfalz und Saarland, Frankfurt am Main (Germany)

    1997-12-01

    The small breeding population of black storks (Ciconia nigra), which had been growing steadily since first nesting in Rhineland-Palantinate in 1982, has been observably decreasing again since 1993, particularly in its main territories. The high mortality of, for the most part, juvenile black storks resulting from collision with a overhead power line (OHL) is described (30 collision victims since the mid-1980s). The energy utilities are called upon to install underground cables on the relevant sections of the power lines in addition to modifying hazardous types of towers in order to reduce the high bird mortality rate. (orig.) [Deutsch] Fuer den seit einer Erstbrut 1982 in Rheinland-Pfalz stetig angestiegenen kleinen Brutbestand des Schwarzstorchs (Ciconia nigra) sind vor allem in seinen Kerngebieten seit 1993 wieder Bestandsrueckgaenge zu verzeichnen. Die hohen Verluste ueberwiegend junger Schwarzstoerche durch Anflug an Mittel- und Niederspannungsfreileitungen (seit Mitte der 80er Jahre 30 Schwarzstoerche als Anflugopfer) werden beschrieben. Neben der Entschaerfung gefaehrlicher Masttypen wird zur Vermeidung der hohen Anflugverluste eine Erdverkabelung der kritischen Leitungsabschnitte gefordert. (orig.)

  7. Expression and Molecular Evolution of Two DREB1 Genes in Black Poplar (Populus nigra)

    Science.gov (United States)

    Chu, Yanguang; Huang, Qinjun; Zhang, Bingyu; Ding, Changjun; Su, Xiaohua

    2014-01-01

    Environmental stresses such as low temperature, drought, and high salinity significantly affect plant growth and yield. As selective forces, these adverse factors play essential roles in shaping phenotypic variation in plant populations. Black poplar (Populus nigra) is an economically and ecologically important forest tree species with widely distributed populations and is thus suitable for experiments detecting evolutionary footprints left by stress. Here, we performed expression and evolutionary analysis of two duplicated DREB A1-subgroup (DREB1) genes, PnDREB68 and PnDREB69, encoding transcription factors that are involved in stress responses. The two genes showed partially overlapping but distinct expression patterns in response to stresses. These genes were strongly and rapidly induced by cold stress in leaves, stems, and roots. In leaf tissue, dehydration stress induced the expression of PnDREB68 but not PnDREB69. PnDREB69 displayed more rapid responses and longer expression durations than PnDREB68 under salt and ABA stress, respectively. Based on single nucleotide polymorphism (SNP) analysis, we found significant population genetic differentiation, with a greater F ST value (0.09189) for PnDREB69 than for PnDREB68 (0.07743). Nucleotide diversity analysis revealed a two-fold higher πT for PnDREB68 than for PnDREB69 (0.00563 vs. 0.00243), reflecting strong purifying selection acting on the former. The results suggest that positive selection acted on PnDREB69, as evidenced by neutral testing using Tajima’s D statistic. The distinct selective forces to which each of the genes was subjected may be associated with expression divergence. Linkage disequilibrium (LD) was low for the sequenced region, with a higher level for PnDREB68 than for PnDREB69. Additionally, analysis of the relationship among carbon isotope ratios, SNP classes and gene expression, together with motif and domain analysis, suggested that 14 polymorphisms within the two genes may be candidates

  8. Polyphenolic content, antiradical activity, stability and microbiological quality of elderberry (Sambucus nigra L.) extracts.

    Science.gov (United States)

    Pliszka, Barbara

    2017-01-01

    The pharmaceutical and food industries expect detailed knowledge on the physicochemical properties of elderberry fruit extracts, their stability and microbiological quality, as well as the polyphenol content in elderberry cultivars. The characteristics of the extracts might be additionally modified by citric acid, which improves the stability of anthocyanins and protects processed fruits and syrups from pathogenic microorganisms. The choice of the method with citric acid was a consequence of the physicochemical charac teristics of elderberry pigments, which are not stable under the effect of light in alcoholic solutions. The aim of study was to analyze the properties of elderberry fruit extracts regarding polyphenol content and antiradical activity, as well as their stability and microbiological quality. The plant material consisted of fruit from four cultivars (Alleso, Korsor, Sampo, Samyl) of black elderberry (Sambucus nigra L.). The following were determined in fruit extracts: polyphe- nolic content (HPLC), antiradical activity (ABTS and DPPH) and stability and microbiological quality. The HPLC analysis of polyphenols demonstrated that the extracts from fruits collected from cv. Samyl had the highest 3-sambubioside cyanidin content and those from cv. Korsor contained the highest quantity of 3-glucoside cyanidin. The extracts from cv. Sampo fruit had a dominant 3-sambubioside-5-gluco- side cyanidin and 3,5-diglucoside cyanidin content. The highest quercetin (5.92 mg 100 mg-1 of extract) and caffeic acid (1.21 mg 100 mg-1 of extract) content was found in fruit extracts from cv. Alleso. The cultivars Samyl and Korsor had a higher level of anthocyanins and higher antiradical activity (ABTS) in fruit extracts than cv. Alleso and Sampo. The antiradical activity (DPPH) of fruit extracts from elderberry cultivars as- sessed in this research was similar. The degradation index for all fruit extracts was similar (DI = 1.035). The microbiological species detected in

  9. Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

    Science.gov (United States)

    Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

    2018-02-28

    Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of

  10. Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

    Science.gov (United States)

    2016-01-01

    The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate

  11. Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

    Science.gov (United States)

    Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

    2011-01-01

    The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

  12. Supplemented Morus nigra extract-based medium associated with FSH enables the survival and growth of isolated ovine secondary ovarian follicles.

    Science.gov (United States)

    Cavalcante, Ayp; Lins, Tlbg; Santos, Jms; Barros, Vrp; Monte, Apo; Barberino, R S; Almeida, Jrgs; Matos, Mht

    2018-04-01

    The effects of Morus nigra ethanolic extract, without or with addition of supplements associated or not with FSH, on in vitro culture of ovine secondary follicles were evaluated. In experiment 1, isolated secondary follicles were cultured for 12 days in α-MEM alone (control) or in different concentrations of M. nigra extract (MN 0.025; 0.05 or 0.1 mg/ml). In experiment 2, culture media were α-MEM supplemented with BSA, insulin, transferrin, selenium, glutamine, hypoxanthine and ascorbic acid (α-MEM + ) or this medium associated with FSH (α-MEM +  + FSH), or 0.1 mg/ml M. nigra without supplements (MN 0.1) or supplemented (MN 0.1 + ) without or with FSH (MN 0.1 +  + FSH). In experiment 1, 0.1 mg/ml M. nigra showed the highest percentages (p nigra extract concentrations. Moreover, MN 0.1 showed lower (p  .05) mitochondrial activity compared to α-MEM. In experiment 2, MN 0.1 +  + FSH showed similar results (p > .05) to α-MEM +  + FSH for all parameters evaluated, except for the daily growth rate, which was higher (p nigra extract (0.1 mg/ml) added by supplements and FSH can be an efficient medium for ovine secondary follicle development. © 2017 Blackwell Verlag GmbH.

  13. Analysis of flavonoids in Rubus erythrocladus and Morus nigra leaves extracts by liquid chromatography and capillary electrophoresis

    Directory of Open Access Journals (Sweden)

    Luciana R. Tallini

    Full Text Available AbstractThis study uses high performance liquid chromatography and capillary electrophoresis as analytical tools to evaluate flavonoids in hydrolyzed leaves extracts of Rubus erythrocladus Mart., Rosaceae, and Morus nigra L., Moraceae. For phytochemical analysis, the extracts were prepared by acid hydrolysis and ultrasonic bath and analyzed by high performance liquid chromatography using an ultraviolet detector and by capillary electrophoresis equipped with a diode-array detector. Quercetin and kaempferol were identified in these extracts. The analytical methods developed were validated and applied. Quercetin and kaempferol were quantified in R. erythrocladus, with 848.43 ± 66.68 μg g-1 and 304.35 ± 17.29 μg g-1, respectively, by HPLC-UV and quercetin, 836.37 ± 149.43 μg g-1, by CE-DAD. In M. nigra the quantifications of quercetin and kaempferol were 2323.90 ± 145.35 μg g-1 and 1446.36 ± 59.00 μg g-1, respectively, by HPLC-UV and, 2552.82 ± 275.30 μg g-1 and 1188.67 ± 99.21 μg g-1, respectively, by CE-DAD. The extracts were also analyzed by ultra-performance liquid chromatography coupled with a diode-array detector and mass spectrometer (MS, UPLC-DAD/MS.

  14. Changes in photosynthesis, mesophyll conductance to CO2, and isoprenoid emissions in Populus nigra plants exposed to excess nickel

    International Nuclear Information System (INIS)

    Velikova, Violeta; Tsonev, Tsonko; Loreto, Francesco; Centritto, Mauro

    2011-01-01

    Poplar (Populus nigra) plants were grown hydroponically with 30 and 200 μM Ni (Ni 30 and Ni 200 ). Photosynthesis limitations and isoprenoid emissions were investigated in two leaf types (mature and developing). Ni stress significantly decreased photosynthesis, and this effect depended on the leaf Ni content, which was lower in mature than in developing leaves. The main limitations to photosynthesis were attributed to mesophyll conductance and metabolism impairment. In Ni-stressed developing leaves, isoprene emission was significantly stimulated. We attribute such stimulation to the lower chloroplastic [CO 2 ] than in control leaves. However chloroplastic [CO 2 ] did not control isoprene emission in mature leaves. Ni stress induced the emission of cis-β-ocimene in mature leaves, and of linalool in both leaf types. Induced biosynthesis and emission of isoprenoids reveal the onset of antioxidant processes that may also contribute to reduce Ni stress, especially in mature poplar leaves. - Graphical abstract: Visible damage caused by Ni treatment. 1 - Ni 0 (control plants); 2 - Ni 200 ; M = mature and D = developing Populus nigra leaves. Display Omitted Highlights: → We study the effect of Ni pollution on photosynthesis and isoprenoid emissions. → Ni stress significantly decreases photosynthesis. The main limitations are attributed to mesophyll conductance and metabolism impairment. → Constitutive isoprene emission was significantly stimulated in Ni-stressed leaves. Exposure to enhanced Ni concentration induces cis-beta-ocimene and linalool emissions. - The study reveals consequences of Ni stress on plant physiology, namely increasing diffusional limitation to photosynthesis and isoprenoid emissions.

  15. Phylogeography of the endangered rosewood Dalbergia nigra (Fabaceae): insights into the evolutionary history and conservation of the Brazilian Atlantic Forest

    Science.gov (United States)

    Ribeiro, R A; Lemos-Filho, J P; Ramos, A C S; Lovato, M B

    2011-01-01

    The Brazilian rosewood (Dalbergia nigra) is an endangered tree endemic to the central Brazilian Atlantic Forest, one of the world's most threatened biomes. The population diversity, phylogeographic structure and demographic history of this species were investigated using the variation in the chloroplast DNA (cpDNA) sequences of 185 individuals from 19 populations along the geographical range of the species. Fifteen haplotypes were detected in the analysis of 1297 bp from two non-coding sequences, trnV-trnM and trnL. We identified a strong genetic structure (FST=0.62, Pclimatic changes in the central part of the Atlantic forest, with cycles of forest expansion and contraction, may have led to repeated vicariance events, resulting in the genetic differentiation of these groups. Based on comparisons among the populations of large reserves and small, disturbed fragments of the same phylogeographic group, we also found evidence of recent anthropogenic effects on genetic diversity. The results were also analysed with the aim of contributing to the conservation of D. nigra. We suggest that the three phylogeographic groups could be considered as three distinct management units. Based on the genetic diversity and uniqueness of the populations, we also indicate priority areas for conservation. PMID:20517347

  16. Effect of ZnO nanoparticles on Brassica nigra seedlings and stem explants: growth dynamics and antioxidative response

    Directory of Open Access Journals (Sweden)

    Hira eZafar

    2016-04-01

    Full Text Available Nanoparticles (NPs have diverse properties in comparison to respective chemicals due to structure, surface area ratio, morphology, and reactivity. Toxicological effects of metallic NPs to organisms including plants have been reported. However, to the authors’ knowledge there is no report on the effect of NPs on in vitro culture of plant explants. In this study, ZnO NPs at 500-1500 mg/L badly affected Brassica nigra seed germination and seedling growth and raised antioxidative activities and antioxidants concentrations. On the other hand, culturing the stem explants of B. nigra on Murashige and Skoog (MS medium in presence of low concentration of ZnO NPs (1-20 mg/L produced white thin roots with thick root hairs. At 10 mg/L ZnO NPs shoots emergence was also observed. The developed calli/roots showed 79% DPPH (2,2-diphenyl-1-picryl hydrazyl radical scavenging activity at 10 mg/L. While total antioxidant and reducing power potential were also significantly different in presence of ZnO NPs. Non enzymatic antioxidative molecules, phenolics (up to 0.15 µg GAE/mg FW and flavonoids (up to 0.22 µg QE/mg FW, also raised and found NPs concentration dependent. We state that ZnO NPs may induce roots from explants cultured on appropriate medium and can be cultured for production of valuable secondary metabolites.

  17. Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion.

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    David Reyes-Corona

    Full Text Available The structural effect of neurturin (NRTN on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system. We showed that the transgenic expression in dopaminergic neurons remained until the end of the study (12 weeks. Only animals expressing NRTN-His showed recovery of tyrosine hydroxylase (TH+ cells (28 ± 2%, their neurites (32 ± 2% and the neuron-specific cytoskeletal marker β-III-tubulin in the substantia nigra; striatal TH(+ fibers were also recovered (52 ± 3%, when compared to the healthy condition. Neurotensin receptor type 1 levels were also significantly recovered in the substantia nigra and striatum. Dopamine recovery was 70 ± 4% in the striatum and complete in the substantia nigra. The number of dendritic spines of striatal medium spiny neurons was also significantly increased, but the recovery was not complete. Drug-activated circling behavior decreased by 73 ± 2% (methamphetamine and 89 ± 1% (apomorphine. Similar decrease was observed in the spontaneous motor behavior. Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion. However, those improvements did not reach the healthy condition, suggesting that NRTN exerts lesser neurotrophic effects than other neurotrophic approaches.

  18. Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report

    Directory of Open Access Journals (Sweden)

    Zangana Hero M

    2011-07-01

    Full Text Available Abstract Background Bilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse. Case presentation We report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission. Conclusion This is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

  19. GABA and Glutamate Synaptic Coadaptations to Chronic Ethanol in the Striatum.

    Science.gov (United States)

    Carlson, Verginia C Cuzon

    2018-02-20

    Alcohol (ethanol) is a widely used and abused drug with approximately 90% of adults over the age of 18 consuming alcohol at some point in their lifetime. Alcohol exerts its actions through multiple neurotransmitter systems within the brain, most notably the GABAergic and glutamatergic systems. Alcohol's actions on GABAergic and glutamatergic neurotransmission have been suggested to underlie the acute behavioral effects of ethanol. The striatum is the primary input nucleus of the basal ganglia that plays a role in motor and reward systems. The effect of ethanol on GABAergic and glutamatergic neurotransmission within striatal circuitry has been thought to underlie ethanol taking, seeking, withdrawal and relapse. This chapter reviews the effects of ethanol on GABAergic and glutamatergic transmission, highlighting the dynamic changes in striatal circuitry from acute to chronic exposure and withdrawal.

  20. Savoring the past: Positive memories evoke value representations in the striatum

    Science.gov (United States)

    Speer, Megan E.; Bhanji, Jamil P.; Delgado, Mauricio R.

    2014-01-01

    Summary Reminders of happy memories can bring back pleasant feelings tied to the original experience, suggesting an intrinsic value in reminiscing about the positive past. However, the neural circuitry underlying the rewarding aspects of autobiographical memory is poorly understood. Using fMRI, we observed enhanced activity during the recall of positive relative to neutral autobiographical memories in corticostriatal circuits that also responded to monetary rewards. Enhanced activity in the striatum and medial prefrontal cortex was associated with increases in positive emotion during recall and striatal engagement further correlated with individual measures of resiliency. Striatal response to the recall of positive memories was greater in individuals whose mood improved after the task. Notably, participants were willing to sacrifice more tangible monetary rewards in order to reminisce about positive past experiences. Our findings suggest that recalling positive autobiographical memories is intrinsically valuable, which may be adaptive for regulating positive emotion and promoting better well-being. PMID:25451197

  1. Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum.

    Science.gov (United States)

    de Oliveira, Iris Machado; Nunes, Brenda Viviane Ferreira; Barbosa, Durán Rafael; Pallares, Alfonso Miguel; Faro, Lilian Rosana Ferreira

    2010-02-15

    Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC. Intrastriatal administration of 1mM or 5mM TMX has not produced significant increases on dopamine (DA) levels, nonetheless the infusion of 10mM TMX increases the DA output to 841+/-132%, when compared to basal levels. Infusion of 1mM CLO has not induced a significant increase in DA levels, even so 2, 3.5 and 5mM CLO have produced an increase of 438+/-8%, 2778+/-598% and 4604+/-516%, respectively, every compared to basal levels. Mecamylamine (MEC), a non-competitive nAChRs antagonist, was used to investigate the role of nAChRs on DA release induced by TMX and CLO. The increases in extracellular DA levels induced by TMX and CLO when associated to MEC are 80% and 68% lower than the effect produced by CLO and TMX isolated. These results confirm that TMX and CLO appear to induce in vivo DA increased release in striatum of rats and it seems to be concentration dependent. Moreover, these results indicate that this effect might be related to nAChRs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  2. Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum.

    Science.gov (United States)

    Muñiz, Javier A; Gomez, Gimena; González, Betina; Rivero-Echeto, María Celeste; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J; Bisagno, Veronica

    2016-05-01

    Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

  3. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    Directory of Open Access Journals (Sweden)

    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  4. Changes in the development of striatum are involved in repetitive behavior in autism.

    Science.gov (United States)

    Langen, Marieke; Bos, Dienke; Noordermeer, Siri D S; Nederveen, Hilde; van Engeland, Herman; Durston, Sarah

    2014-09-01

    Repetitive behavior is a core feature of autism and has been linked to differences in striatum. In addition, the brain changes associated with autism appear to vary with age. However, most studies investigating striatal differences in autism are cross-sectional, limiting inferences on development. In this study, we set out to 1) investigate striatal development in autism, using a longitudinal design; and 2) examine the relationship between striatal development and repetitive behavior. We acquired longitudinal structural magnetic resonance imaging scans from 86 individuals (49 children with autism, 37 matched control subjects). Each individual was scanned twice, with a mean scan interval time of 2.4 years. Mean age was 9.9 years at time 1 and 12.3 years at time 2. Striatal structures were traced manually with high reliability. Multivariate analyses of variance were used to investigate differences in brain development between diagnostic groups. To examine the relationship with behavior, correlations between changes in brain volumes and clinical measures were calculated. Our results showed an increase in the growth rate of striatal structures for individuals with autism compared with control subjects. The effect was specific to caudate nucleus, where growth rate was doubled. Second, faster striatal growth was correlated with more severe repetitive behavior (insistence on sameness) at the preschool age. This longitudinal study of brain development in autism confirms the involvement of striatum in repetitive behavior. Furthermore, it underscores the significance of brain development in autism, as the severity of repetitive behavior was related to striatal growth, rather than volume per se. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Effects of Ventral Striatum Lesions on Stimulus-Based versus Action-Based Reinforcement Learning.

    Science.gov (United States)

    Rothenhoefer, Kathryn M; Costa, Vincent D; Bartolo, Ramón; Vicario-Feliciano, Raquel; Murray, Elisabeth A; Averbeck, Bruno B

    2017-07-19

    Learning the values of actions versus stimuli may depend on separable neural circuits. In the current study, we evaluated the performance of rhesus macaques with ventral striatum (VS) lesions on a two-arm bandit task that had randomly interleaved blocks of stimulus-based and action-based reinforcement learning (RL). Compared with controls, monkeys with VS lesions had deficits in learning to select rewarding images but not rewarding actions. We used a RL model to quantify learning and choice consistency and found that, in stimulus-based RL, the VS lesion monkeys were more influenced by negative feedback and had lower choice consistency than controls. Using a Bayesian model to parse the groups' learning strategies, we also found that VS lesion monkeys defaulted to an action-based choice strategy. Therefore, the VS is involved specifically in learning the value of stimuli, not actions. SIGNIFICANCE STATEMENT Reinforcement learning models of the ventral striatum (VS) often assume that it maintains an estimate of state value. This suggests that it plays a general role in learning whether rewards are assigned based on a chosen action or stimulus. In the present experiment, we examined the effects of VS lesions on monkeys' ability to learn that choosing a particular action or stimulus was more likely to lead to reward. We found that VS lesions caused a specific deficit in the monkeys' ability to discriminate between images with different values, whereas their ability to discriminate between actions with different values remained intact. Our results therefore suggest that the VS plays a specific role in learning to select rewarded stimuli. Copyright © 2017 the authors 0270-6474/17/376902-13$15.00/0.

  6. The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples

    NARCIS (Netherlands)

    Pennartz, C.M.A.; Lee, E.; Verheul, J.; Lipa, P.; Barnes, C.A.; Mc. Naughton, B.L.

    2004-01-01

    Previously it has been shown that the hippocampus and neocortex can spontaneously reactivate ensemble activity patterns during post-behavioral sleep and rest periods. Here we examined whether such reactivation also occurs in a subcortical structure, the ventral striatum, which receives a direct

  7. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in

  8. Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

    DEFF Research Database (Denmark)

    Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

    2013-01-01

    Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

  9. Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training.

    Science.gov (United States)

    Bello-Medina, Paola C; Flores, Gonzalo; Quirarte, Gina L; McGaugh, James L; Prado Alcalá, Roberto A

    2016-10-18

    A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

  10. Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington's disease mice.

    Science.gov (United States)

    Achour, Mayada; Le Gras, Stéphanie; Keime, Céline; Parmentier, Frédéric; Lejeune, François-Xavier; Boutillier, Anne-Laurence; Néri, Christian; Davidson, Irwin; Merienne, Karine

    2015-06-15

    Huntington's disease (HD) is a neurodegenerative disease associated with extensive down-regulation of genes controlling neuronal function, particularly in the striatum. Whether altered epigenetic regulation underlies transcriptional defects in HD is unclear. Integrating RNA-sequencing (RNA-seq) and chromatin-immunoprecipitation followed by massively parallel sequencing (ChIP-seq), we show that down-regulated genes in HD mouse striatum associate with selective decrease in H3K27ac, a mark of active enhancers, and RNA Polymerase II (RNAPII). In addition, we reveal that decreased genes in HD mouse striatum display a specific epigenetic signature, characterized by high levels and broad patterns of H3K27ac and RNAPII. Our results indicate that this signature is that of super-enhancers, a category of broad enhancers regulating genes defining tissue identity and function. Specifically, we reveal that striatal super-enhancers display extensive H3K27 acetylation within gene bodies, drive transcription characterized by low levels of paused RNAPII, regulate neuronal function genes and are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Together, our results provide evidence for preferential down-regulation of genes controlled by super-enhancers in HD striatum and indicate that enhancer topography is a major parameter determining the propensity of a gene to be deregulated in a neurodegenerative disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

    Science.gov (United States)

    Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

    2008-04-01

    Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (Self-ratings of alcohol craving. The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

  12. Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders.

    Science.gov (United States)

    Rapanelli, M; Frick, L; Pogorelov, V; Ohtsu, H; Bito, H; Pittenger, C

    2017-01-24

    Tic disorders affect ~5% of the population and are frequently comorbid with obsessive-compulsive disorder, autism, and attention deficit disorder. Histamine dysregulation has been identified as a rare genetic cause of tic disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene represent a promising pathophysiologically grounded model. How alterations in the histamine system lead to tics and other neuropsychiatric pathology, however, remains unclear. We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice. The H3 receptor has significant basal activity even in the absence of ligand and thus may modulate striatal function in this knockout model. We probed H3R function using specific agonists. The H3 agonists R-aminomethylhistamine (RAMH) and immepip produced behavioral stereotypies in KO mice, but not in controls. H3 agonist treatment elevated intra-striatal dopamine in KO mice, but not in controls. This was associated with elevations in phosphorylation of rpS6, a sensitive marker of neural activity, in the dorsal striatum. We used a novel chemogenetic strategy to demonstrate that this dorsal striatal activity is necessary and sufficient for the development of stereotypy: when RAMH-activated cells in the dorsal striatum were chemogenetically activated (in the absence of RAMH), stereotypy was recapitulated in KO animals, and when they were silenced the ability of RAMH to produce stereotypy was blocked. These results identify the H3 receptor in the dorsal striatum as a contributor to repetitive behavioral pathology.

  13. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

    Science.gov (United States)

    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-03-01

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration. The present study, therefore, compares the effects of 10 and 60-day self-administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self-administration was found for 6 IEGs in dorsal and ventral striatum (c-fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long-term sucrose self-administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self-administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short-term and long-term self-administration. These steady changes in IEG expression are, therefore, associated with stable self-administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use. © 2015 Society for the Study of Addiction.

  14. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    Directory of Open Access Journals (Sweden)

    Hiroaki Kawamichi

    2016-11-01

    Full Text Available Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68. Furthermore, we also conducted a voxel-based morphometry (VBM study of the effects of being in a romantic relationship (N = 113. Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

  15. Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

    Science.gov (United States)

    Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68). Furthermore, we also conducted a voxel-based morphometry study of the effects of being in a romantic relationship (N = 113). Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward. PMID:27895606

  16. Underground riparian wood: Buried stem and coarse root structures of Black Poplar (Populus nigra L.)

    Science.gov (United States)

    Holloway, James V.; Rillig, Matthias C.; Gurnell, Angela M.

    2017-02-01

    Despite the potential importance of tree species in influencing the processes of wood recruitment, transport, retention, and decay that control river wood budgets, focus has been relatively limited on this theme within fluvial wood research. Furthermore, one of the least investigated topics is the belowground living wood component of riparian trees. This paper presents observations of the morphology and age of buried stem and coarse root structures of eight Populus nigra individuals located in the riparian woodland of two sites on the middle to lower Tagliamento River, Italy. This species was selected because of its wide distribution along European rivers and its frequent dominance of riparian woodland. Each tree was excavated by hand to expose a minimum of half of the root system with complete exposure of the main axis. Smaller roots were then removed and larger protruding roots cut back to permit access to the main axis. The excavated structures were photographed from multiple angles for photogrammetric modelling; the structure and character of the exposed sediments around the tree's main axis were recorded; and wood samples were taken from the main aboveground stem(s), sections of the main buried axis, and major roots for dendrochronological analysis. Results from these field observations and laboratory dating of the wood samples were combined to describe the belowground morphology of each tree and to draw inferences concerning the impact of fluvial disturbances. Common features of these excavated structures included: (i) rooting depths to below the bar surface where the original tree established, with many young roots also existing at depth; (ii) translocation of the main buried axis in a downstream direction; (iii) a main buried axis comprised mainly of stems that have become buried and then generated new shoots, including multistem patches, and adventitious roots; (iv) the presence of steps and bends in the main buried axis associated with the generation of

  17. Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.

    Science.gov (United States)

    Stayte, Sandy; Rentsch, Peggy; Tröscher, Anna R; Bamberger, Maximilian; Li, Kong M; Vissel, Bryce

    2017-01-01

    Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.

  18. DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Kazuko Takahashi-Niki

    2015-03-01

    Full Text Available Parkinson's disease (PD is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1 mg/kg of compound-23 and then with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP at 1 h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.

  19. The ethylene-inhibitor aminoethoxyvinylglycine restores normal nodulation by Rhizobium leguminosarum biovar. viciae on Vicia sativa subsp. nigra by suppressing the 'Thick and short roots' phenotype

    NARCIS (Netherlands)

    Zaat, S. A.; van Brussel, A. A.; Tak, T.; Lugtenberg, B. J.; KIJNE, J. W.

    1989-01-01

    Nodulation of Vicia sativa subsp. nigra L. by Rhizobium bacteria is coupled to the development of thick and short roots (Tsr). This root phenotype as well as root-hair induction (Hai) and root-hair deformation (Had) are caused by a factor(s) produced by the bacteria in response to plant flavonoids.

  20. Species delimitation in asexual insects of economic importance: The case of black scale (Parasaissetia nigra, a cosmopolitan parthenogenetic pest scale insect.

    Directory of Open Access Journals (Sweden)

    Yen-Po Lin

    Full Text Available Asexual lineages provide a challenge to species delimitation because species concepts either have little biological meaning for them or are arbitrary, since every individual is monophyletic and reproductively isolated from all other individuals. However, recognition and naming of asexual species is important to conservation and economic applications. Some scale insects are widespread and polyphagous pests of plants, and several species have been found to comprise cryptic species complexes. Parasaissetia nigra (Nietner, 1861 (Hemiptera: Coccidae is a parthenogenetic, cosmopolitan and polyphagous pest that feeds on plant species from more than 80 families. Here, we implement multiple approaches to assess the species status of P. nigra, including coalescence-based analyses of mitochondrial and nuclear genes, and ecological niche modelling. Our results indicate that the sampled specimens of P. nigra should be considered to comprise at least two ecotypes (or "species" that are ecologically differentiated, particularly in relation to temperature and moisture. The presence of more than one ecotype under the current concept of P. nigra has implications for biosecurity because the geographic extent of each type is not fully known: some countries may currently have only one of the biotypes. Introduction of additional lineages could expand the geographic extent of damage by the pest in some countries.

  1. On-line detection of root-induced volatiles in Brassica nigra plants infested with Delia radicum L. root fly larvae

    NARCIS (Netherlands)

    Crespo, E.; Hordijk, C.A.; de Graaf, R.; Samudrala, D.; Cristescu, S.M.; Harren, F.J.M.; Van Dam, N.M.

    2012-01-01

    Plants emit various volatile organic compounds (VOCs) upon herbivore attack. These VOC emissions often show temporal dynamics which may influence the behavior of natural enemies using these volatiles as cues. This study analyzes on-line VOC emissions by roots of Brassica nigra plants under attack by

  2. Status of black walnut (Juglans nigra L.) in the Eastern United States in light of the discovery of thousand cankers disease

    Science.gov (United States)

    KaDonna Randolph; Anita Rose; Christopher Oswalt; Mark Brown

    2013-01-01

    Juglans nigra (black walnut) is widely distributed throughout the US eastern forest, with high concentrations occurring in Missouri and the Ohio and Tennessee River basins. It is an extremely desirable tree for wildlife forage and timber production on forest land, and for shade, aesthetics, and wildlife forage in urban areas. Current (2009–2010)...

  3. Pressurized hot water extraction followed by high-performance liquid chromatography for determination of polyphenols in Sambucus nigra L. branches in dependence on vegetative period of the plant

    Czech Academy of Sciences Publication Activity Database

    Hohnová, Barbora; Šalplachta, Jiří; Karásek, Pavel

    2017-01-01

    Roč. 56, č. 3 (2017), s. 299-303 ISSN 1336-8672 R&D Projects: GA ČR(CZ) GA16-03749S Institutional support: RVO:68081715 Keywords : PHWE * polyphenols * Sambucus nigra L. branches Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 1.950, year: 2016

  4. Pressurized hot water extraction followed by high-performance liquid chromatography for determination of polyphenols in Sambucus nigra L. branches in dependence on vegetative period of the plant

    Czech Academy of Sciences Publication Activity Database

    Hohnová, Barbora; Šalplachta, Jiří; Karásek, Pavel

    2017-01-01

    Roč. 56, č. 3 (2017), s. 299-303 ISSN 1336-8672 R&D Projects: GA ČR(CZ) GA16-03749S Institutional support: RVO:68081715 Keywords : PHWE * polyphenols * Sambucus nigra L. branches Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 1.950, year: 2016

  5. Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

    Science.gov (United States)

    Siessmeier, Thomas; Kienast, Thorsten; Wrase, Jana; Larsen, Jennifer Lynne; Braus, Dieter F; Smolka, Michael N; Buchholz, Hans Georg; Schreckenberger, Mathias; Rösch, Frank; Cumming, Paul; Mann, Karl; Bartenstein, Peter; Heinz, Andreas

    2006-07-01

    Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[(18)F]fluoro-l-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes elicited by standardized affectively positive, negative and neutral visual stimuli. The magnitude of in the ventral striatum was positively correlated with BOLD signal increases in the left anterior cingulate cortex and right insular operculum elicited by positive vs. neutral stimuli, but not negative vs. neutral stimuli. In the dorsal striatum, the magnitude of was positively correlated with processing of positive and negative stimuli in the left dorsolateral prefrontal cortex. These findings suggest that dopamine synthesis capacity in the ventral striatum correlates with the attentional processing of rewarding positive stimuli in the anterior cingulate cortex of healthy subjects. Dopaminergic neurotransmission in the associative dorsal striatum has been associated previously with habit learning. The observed correlation between dopamine synthesis capacity in the dorsal striatum and BOLD signal changes in the dorsolateral prefrontal cortex suggests dopaminergic modulation of processing of emotional stimuli in brain areas associated with motor planning and executive behaviour control.

  6. Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

    Science.gov (United States)

    Kathirvelu, Balachandar; Colombo, Paul J

    2013-11-01

    Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  7. Peripheral inflamation-induced increase of AMPA-mediated currents and Ca2+ transients in the presence of cyclothiazide in the rat substantia gelatinosa neurons.

    Science.gov (United States)

    Voitenko, N; Gerber, G; Youn, D; Randic, M

    2004-05-01

    This study employing a rodent model of acute pain investigated the influence of carrageenan-induced inflammation on the ability of S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation to induce membrane currents and rises in cytosolic free calcium concentration ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole-cell patch-clamp recording and fura-2 calcium imaging in spinal cord slices of L4-L5 segments. The novel finding of this study is that carrageenan-induced inflammation, in the presence of cyclothiazide, an inhibitor of AMPA receptor desensitization, produces a sustained facilitation of the AMPA-mediated membrane current and rises in [Ca2+]i in both the soma and proximal dendrites of SG neurons recorded on the injected side 3 h after the induction of inflammation. These results suggest that in carrageenan-inflamed rats AMPA receptors undergo some alterations that influence AMPA receptors desensitization and/or sensitivity to cyclothiazide.

  8. Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation

    DEFF Research Database (Denmark)

    Christophersen, Nicolai S.; Gronborg, Mette; Petersen, Thomas Nordahl

    2007-01-01

    upregulation with increased positive staining of cell bodies in the SNc and fibers in the striatum. Analysis of the developmental regulation of Dlk1 in the murine ventral midbrain showed that the upregulation of Dlk1 mRNA correlated with the generation of tyrosine hydroxylase (TH)-positive neurons. Furthermore......Affymetrix GeneChip technology and quantitative real-time PCR (Q-PCR) were used to examine changes in gene expression in the adult murine substantia nigra pars compacta (SNc) following lentiviral glial cell line-derived neurotrophic factor (GDNF) delivery in adult striatum. We identified several......, Dlk1 expression was analyzed in MesC2.10 cells, which are derived from embryonic human mesencephalon and capable of undergoing differentiation into dopaminergic neurons. We detected upregulation of Dlk1 mRNA and protein under conditions where MesC2.10 cells differentiate into a dopaminergic phenotype...

  9. Evaluation of Internal Cracks and Collapse in Poplar Wood (Populus nigra during a Conventional Drying Process with Ultrasonic Inspection

    Directory of Open Access Journals (Sweden)

    Saeid ESHAGHI

    2012-05-01

    Full Text Available In this research, internal cracks and collapse of wood, formed during drying process, were measured using ultrasonic inspection. For this purpose, seven poplar (Populus nigra small blocks were dried, according to a time-based schedule. Ultrasonic waves� propagation velocity was measured at both parallel and perpendicular to grain directions, using Sylvatest ultrasound device, during kiln drying process. Results showed that in all dried blocks, waves� propagation velocity in the parallel direction was higher than in the perpendicular direction to grain. Ultrasonic waves� propagation test for non-destructive identification of internal cracks, which occurs in wood during drying process in the parallel direction, was more successful compared to the perpendicular direction. Using ultrasonic waves� propagation test for detection of collapse that occurs in wood during drying process was not useful.

  10. Black poplar-tree (Populus nigra L.) bark as an alternative indicator of urban air pollution by chemical elements

    International Nuclear Information System (INIS)

    Berlizov, A.N.; Malyuk, I.A.; Tryshyn, V.V.

    2008-01-01

    Capabilities of black poplar-tree (Populus nigra L.) bark as a biomonitor of atmospheric air pollution by chemical elements were tested against epiphytic lichens Xanthoria parietina (L.) and Physcia adscendens (Fr.). Concentrations of 40 macro and trace elements were determined using epicadmium and instrumental NAA. The data obtained were processed using non-parametric tests. A good correlation was found between concentrations of majority of elements in bark and lichens. On the accumulation capability bark turned out to be competitive with both lichens examined. The main inorganic components of black poplar-tree bark were revealed. A substrate influence on the concentrations of some elements in epiphytic lichens was established. An optimized procedure of bark pre-irradiation treatment was suggested. (author)

  11. Essential oils of Pinus nigra J.F. Arnold subsp. laricio Maire: Chemical composition and study of their herbicidal potential

    Directory of Open Access Journals (Sweden)

    Ismail Amri

    2017-05-01

    Full Text Available The chemical composition of essential oils isolated by hydrodistillation from the needles of Tunisian Pinus nigra L. subsp. laricio was analyzed by GC and GC/MS. 27 compounds were identified, representing 97.9% of total oil, which was found to be rich in oxygenated diterpenes (38.5% particularly manool oxide (38% and sesquiterpene hydrocarbons (41.4% that included germacrene D (16.7%, δ-cadinene (9% and (E-caryophyllene (8.9%. Results of the herbicidal effects of the oil when tested on Phalaris canariensis L., Trifolium campestre Schreb. and Sinapis arvensis L., indicated that the oil completely inhibited germination and seedling growth at a high concentration (5 μL/mL−1, while at low doses the oil acted by decreasing germination and partially inhibiting seedling growth of all tested weeds.

  12. Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

    Science.gov (United States)

    Diederen, Kelly M J; Ziauddeen, Hisham; Vestergaard, Martin D; Spencer, Tom; Schultz, Wolfram; Fletcher, Paul C

    2017-02-15

    Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness. SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that

  13. The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking

    Science.gov (United States)

    Darcq, Emmanuel; Morisot, Nadege; Phamluong, Khanhky; Warnault, Vincent; Jeanblanc, Jerome; Longo, Frank M.; Massa, Stephen M.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) keeps alcohol intake in moderation. For example, activation of the BDNF receptor tropomyosin receptor kinase B (TrkB) in the DLS reduces intake in rats that consume moderate amounts of alcohol. Here, we tested whether long-term excessive consumption of alcohol produces neuroadaptations in BDNF signaling in the rat DLS. We found that BDNF was no longer able to gate alcohol self-administration after a history of repeated cycles of binge alcohol drinking and withdrawal. We then elucidated the possible neuroadaptations that could block the ability of BDNF to keep consumption of alcohol in moderation. We report that intermittent access to 20% alcohol in a two-bottle choice paradigm that models excessive alcohol drinking produces a mobilization of DLS p75 neurotrophin receptor (p75NTR), whose activities oppose those of the Trk receptors, including TrkB. These neuroadaptations were not observed in the DLS of rats exposed to continuous access to 10% alcohol or in rats consuming sucrose. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of the p75NTR gene in the DLS, as well as intra-DLS infusion or systemic administration of the p75NTR modulator, LM11A-31, significantly reduced binge drinking of alcohol. Together, our results suggest that excessive alcohol consumption produces a change in BDNF signaling in the DLS, which is mediated by the recruitment of p75NTR. Our data also imply that modulators of p75NTR signaling could be developed as medications for alcohol abuse disorders. SIGNIFICANCE STATEMENT Neuroadaptations gate or drive excessive, compulsive alcohol drinking. We previously showed that brain-derived neurotrophic factor and its receptor, TrkB, in the dorsolateral striatum (DLS), are part of an endogenous system that keeps alcohol drinking in moderation. Here, we show that a history of excessive alcohol intake produces neuroadaptations in the DLS that preclude BDNF

  14. Regionally distinct phasic dopamine release patterns in the striatum during reversal learning.

    Science.gov (United States)

    Klanker, Marianne; Fellinger, Lisanne; Feenstra, Matthijs; Willuhn, Ingo; Denys, Damiaan

    2017-03-14

    Striatal dopamine (DA) plays a central role in reward-related learning and behavioral adaptation to changing environments. Recent studies suggest that rather than being broadcast as a uniform signal throughout the entire region, DA release dynamics diverge between different striatal regions. In a previous study, we showed that phasic DA release patterns in the ventromedial striatum (VMS) rapidly adapt during reversal learning. However, it is unknown how DA dynamics in the dorsolateral striatum (DLS) are modulated during such adaptive behavior. Here, we used fast-scan cyclic voltammetry to measure phasic DA release in the DLS during spatial reversal learning. In the DLS, we observed minor DA release after the onset of a visual cue signaling reward availability, followed by more pronounced DA release during more proximal reward cues (e.g., lever extension) and execution of the operant response (i.e., lever press), both in rewarded and non-rewarded trials. These release dynamics (minor DA after onset of the predictive visual cue, prominent DA during the operant response) did not change significantly during or following a reversal of response-reward contingencies. Notably, the DA increase to the lever press did not reflect a general signal related to the initiation of any motivated motor response, as we did not observe DA release when rats initiated nose pokes into the food receptacle during inter-trial intervals. This suggests that DA release in the DLS occurs selectively during the initiation and execution of a learned operant response. Together with our previous results obtained in the VMS, these findings reveal distinct phasic DA release patterns during adaptation of established behavior in DLS and VMS. The VMS DA signal, which is highly sensitive to reversal of response-reward contingences, may provide a teaching signal to guide reward-related learning and facilitate behavioral adaptation, whereas DLS DA may reflect a 'response execution signal' largely

  15. In Vivo Assessment of Antihyperglycemic and Antioxidant Activity from Oil of Seeds of Brassica Nigra in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2013-08-01

    Full Text Available Purpose: This study was made to investigate the antihyperglycemic and antioxidant potential of oil of seeds of Brassica nigra (BNO in streptozotocin -nicotinamide (STZ induced type 2 diabetic rats. Methods: BNO was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic study. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results: Administration of BNO at a dose 500 mg/kg and 1000 mg/kg body weight p.o. to STZ diabetic rats showed reduction in blood glucose level from 335 mg/dl to 280 mg/dl at 4th h and from 330 mg/dl to 265 mg/dl respectively which was found significant (p<0.01 as compared with diabetic control. BNO (500 mg/kg and 1000 mg/kg and glibenclamide (0.6 mg/kg in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-nicotinamide induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in glycosylated hemoglobin in test groups as compared to control group. In vivo antioxidant studies on STZ-nicotinamide induced diabetic rat’s revealed decreased malondialdehyde (MDA and increased reduced glutathione (GSH. Conclusion: Thus the results showed that the oil of seeds of Brassica nigra has significant antihyperglycemic and antioxidant activity.

  16. Host ranges of gregarious muscoid fly parasitoids: Muscidifurax raptorellus (Hymenoptera: Pteromalidae), Tachinaephagus zealandicus (Hymenoptera: Encyrtidae), and Trichopria nigra (Hymenoptera: Diapriidae).

    Science.gov (United States)

    Geden, Christopher J; Moon, Roger D

    2009-06-01

    Attack rates, progeny production, sex ratios, and host utilization efficiency of Muscidifurax raptorellus (Kogan and Legner) (Hymenoptera: Pteromalidae), Tachinaephagus zealandicus Ashmead (Hymenoptera: Encyrtidae), and Trichopria nigra (Nees) (Hymenoptera: Diapriidae) were evaluated in laboratory bioassays with five dipteran hosts: house fly (Musca domestica L.), stable fly (Stomoxys calcitrans L.), horn fly (Hematobia irritans L.), black dump fly [Hydrotaea aenescens (Weidemann)] (Diptera: Muscidae), and a flesh fly (Sarcophaga bullata Parker) (Diptera: Sarcophagidae). M. raptorellus killed and successfully parasitized all five host species and produced an average 2.6 parasitoid progeny from each host. Host attack rates were highest on stable fly and lowest on horn fly; there were no differences among hosts in the total number of progeny produced. T. zealandicus killed larvae of all fly host species in similar numbers, but parasitism was most successful on H. aenescens and S. bullata and least successful on horn fly and house fly hosts. Significantly more parasitoid progeny emerged from S. bullata (10.2 parasitoids per host) than the other hosts; only 2.5 progeny were produced from parasitized horn fly hosts. Most of the killed puparia that produced neither adult flies nor parasitoids ("duds") contained dead parasitoids; in house fly, stable fly, and horn fly hosts, >30% of these dudded pupae contained adult wasps that failed to eclose. T. nigra successfully parasitized pupae of all host species except house fly and was most successful on stable fly. Significantly more parasitoid progeny emerged from S. bullata (30.6 parasitoids per host) than the other hosts; only 5.7 progeny were produced from horn fly hosts.

  17. Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

    Science.gov (United States)

    Holubiec, Mariana I; Romero, Juan I; Blanco, Eduardo; Tornatore, Tamara Logica; Suarez, Juan; Rodríguez de Fonseca, Fernando; Galeano, Pablo; Capani, Francisco

    2017-07-13

    Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

    Science.gov (United States)

    Holz, Nathalie E; Boecker-Schlier, Regina; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2017-02-01

    Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Yearning for connection? Loneliness is associated with increased ventral striatum activity to close others.

    Science.gov (United States)

    Inagaki, Tristen K; Muscatell, Keely A; Moieni, Mona; Dutcher, Janine M; Jevtic, Ivana; Irwin, Michael R; Eisenberger, Naomi I

    2016-07-01

    Loneliness is a distressing state indicating that one's basic need for social connection is not being met. In an effort to satisfy the need for social connection, loneliness may increase the processing of social cues and desire to connect with others. Yet the neural substrates that contribute to the drive for increased connection in response to loneliness are not known. The ventral striatum (VS), previously shown to increase in response to craving food and other rewarding stimuli, may contribute to "social craving" when one is lonely. That is, the VS may track one's 'hunger' for reconnection much as it tracks hunger for food. To examine this, participants reported on their feelings of loneliness before undergoing an fMRI scan where they viewed cues of potential social reconnection (images of a close other). Consistent with the hypothesis that loneliness stems from an unmet need for connection, loneliness was associated with reduced feelings of connection with the close other. Furthermore, greater reported loneliness was associated with increased VS activity to viewing a close other (vs stranger). Results extend the current literature by showing that lonely individuals show increased activity in reward-related regions to their closest loved ones, possibly reflecting an increased desire for social connection. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

    International Nuclear Information System (INIS)

    Goeders, N.E.; Kuhar, M.J.

    1987-01-01

    A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of [ 3 H]sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems

  1. Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics

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    Daniil eSarkisyan

    2015-05-01

    Full Text Available The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels of prodynorphin (PDYN and proenkephalin (PENK mRNAs (by qRT-PCR, and dynorphins and enkephalins (by radioimmunoassay in the caudate nucleus and putamen between alcoholics and control subjects. We also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects PDYN expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. PDYN mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while PDYN mRNA and Leu-enkephalin-Arg, a marker of PDYN were decreased in the putamen of alcoholics carrying high risk rs1997794 C allele. Downregulation of opioid peptides in the dorsal striatum may contribute to development of alcoholism including changes in goal directed behavior and formation of a compulsive habit in alcoholics.

  2. Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

    Science.gov (United States)

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2017-04-01

    The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Interest in politics modulates neural activity in the amygdala and ventral striatum.

    Science.gov (United States)

    Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

    2010-11-01

    Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

  4. Huntington disease: a single-gene degenerative disorder of the striatum.

    Science.gov (United States)

    Nopoulos, Peggy C

    2016-03-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

  5. [The action of epidermal growth factor on the development of cultured striatum cells].

    Science.gov (United States)

    Castillo-Díaz, L; Castellano-Benítez, O; Soto-Alonso, J; Rosillo-Martí, J C; de la Cuétara-Bernal, K

    1997-10-01

    Epidermic growth factor (EGF) has a neurotrophic mitogenic effect on different cell populations in the nervous system. This is modulated by the stage of development and microenvironment of the cells. In this paper we describe the action of EGF on embryonic striatum cells of a culture system dissociated from neurons and glias. The cell culture is prepared from 16-17 day rat embryos. In the system used, the cell population was cultured for 20-24 hours in a medium containing serum. This medium was later replaced by a mixture of specific nutrients and treated for 6 days with 20 mg/ml of EGF. The substitution of serum during the initial period of development led to an appreciable reduction in the living cells in the treated cultures and in the controls. The surviving cells were mainly cellular precursors, taking into account their morphological characteristics and capacity for proliferation. The effect of EGF was seen in an increase in the number of cells and was shown to be a stimulus to the proliferation of neuronal and astrocyte precursors. The specific activity of choline acetyl-transferases determined in the cultures at 16 days showed differentiation of a cholinergic neurons subpopulation, which responded to treatment with nerve growth factor with an increase in the activity of this enzyme.

  6. Tetrodotoxin effects in the stimulated acetylcholine release by agonist of glutamate in mice striatum tissue

    International Nuclear Information System (INIS)

    Paes, Paulo Cesar de Arruda; Camillo, Maria A.P.; Rogero, Jose Roberto; Troncone, Lanfranco R.P.

    2002-01-01

    The toxins of animal venoms have been used as important tools for biochemical studies of physiological and pathological processes of diverse systems. In this work we used the action of tetrodotoxin on sodium channels to map the localization of glutamate receptors in cholinergic neurons from striatum tissue of rats. All glutamate receptors are exciting, so they promote the release of other neurotransmitters. In this work we focus on acetylcholine. The localization of glutamate receptor, on the soma or on the excitatory terminal, may contribute for a better understanding of its function. For this work we applied the in vitro method of tritiated neurotransmitter release. The agonists of glutamate receptors chosen were glutamic acid 500μM, NMDA 100μM, kainic acid 300μM, quisqualic acid 300μM and AMPA 1mM. In the first part of the assay the basal and stimulated releases were measured and in the second, the same protocol was performed in the presence of tetrodotoxin 1μM. The reductions observed in basal and stimulated release in the presence of tetrodotoxin suggested that the receptors type AMPA and NMDA were located in soma of cholinergic cell preferentially and the other ones presented a more equilibrate distribution among the axons and the soma. (author)

  7. Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

    Directory of Open Access Journals (Sweden)

    Ulrich eKirk

    2015-02-01

    Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

  8. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  9. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    Full Text Available Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase, breakdown (catechol-O-methyl transferase; monoamine oxygenase, transport [vesicular monoamine transporter (VMAT, dopamine transporter (DAT] and receptors (DRD1-D5] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen

  10. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    Science.gov (United States)

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  11. Dopamine release in ventral striatum during Iowa Gambling Task performance is associated with increased excitement levels in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Møller, Arne; Peterson, Ericka

    2011-01-01

    Aims Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls. Design Pathological Gamblers...... and Healthy Controlswere experimentally compared in a non-gambling (baseline) and gambling condition. Measurements We used Positron Emission Tomography (PET) with the tracer raclopride to measure dopamine D 2/3 receptor availability in the ventral striatum during a non-gambling and gambling condition...... of the Iowa GamblingTask (IGT). After each condition participants rated their excitement level. Setting Laboratory experiment. Participants 18 Pathological Gamblers and 16 Healthy Controls. Findings Pathological Gamblers with dopamine release in the ventral striatum had significantly higher excitement levels...

  12. Glucocorticoid administration into the dorsolateral but not dorsomedial striatum accelerates the shift from a spatial toward procedural memory.

    Science.gov (United States)

    Siller-Pérez, Cristina; Serafín, Norma; Prado-Alcalá, Roberto A; Roozendaal, Benno; Quirarte, Gina L

    2017-05-01

    Glucocorticoid stress hormones are known to enhance the consolidation of hippocampus-dependent spatial and contextual memory. Recent findings indicate that glucocorticoids also enhance the consolidation of procedural memory that relies on the dorsal striatum. The dorsal striatum can be functionally subdivided into the dorsolateral striatum (DLS), which is primarily implicated in shaping procedural memories, and the dorsomedial striatum (DMS), which is engaged in spatial memory. Here, we investigated the hypothesis that posttraining glucocorticoid administration into the DLS promotes the formation of a procedural memory that will normally take place only with extensive training. Male Wistar rats were trained to find a reward in a cross maze that can be solved through either place or response learning. Rats received four trials per day for 5days, a probe trial on Day 6, further training on Days 7-13, and an additional probe trial on Day 14. On Days 2-4 of training, they received posttraining infusions of corticosterone (10 or 30ng) or vehicle into either the DLS or DMS. Rats treated with vehicle into either the DLS or DMS displayed place learning on Day 6 and response learning on Day 14, indicating a shift in control of learned behavior toward a habit-like procedural strategy with extended training. Rats administered corticosterone (10ng) into the DLS displayed response learning on both Days 6 and 14, indicating an accelerated shift to response learning. In contrast, corticosterone administered posttraining into the DMS did not significantly alter the shift from place to response learning. These findings indicate that glucocorticoid administration into the DLS enhances memory consolidation of procedural learning and thereby influences the timing of the switch from the use of spatial/contextual memory to habit-like procedural memory to guide behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

    Science.gov (United States)

    Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W

    2012-06-20

    Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

  14. Nicotine-induced and D1-receptor-dependent dendritic remodeling in a subset of dorsolateral striatum medium spiny neurons.

    Science.gov (United States)

    Ehlinger, Daniel G; Burke, Julian C; McDonald, Craig G; Smith, Robert F; Bergstrom, Hadley C

    2017-07-25

    Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (at least 21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of these subpopulations revealed that DLS MSNs with more primary dendrites were selectively remodeled by chronic nicotine exposure and remodeling was specific to the distal-most portions of the dendritic arbor. Co-administration of the dopamine D1 receptor (D1R) antagonist SCH23390 completely reversed the selective effects of nicotine on DLS MSN dendrite morphology, supporting a causal role for dopamine signaling at D1 receptors in nicotine-induced dendrite restructuring. Considering the functional importance of the DLS in shaping and expressing habitual behavior, these data support a model in which nicotine induces persistent and selective changes in the circuit connectivity of the DLS that may promote and sustain addiction-related behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze

    Science.gov (United States)

    Gardner, Robert S.; Suarez, Daniel F.; Robinson-Burton, Nadira K.; Rudnicky, Christopher J.; Gulati, Asish; Ascoli, Giorgio A.; Dumas, Theodore C.

    2016-01-01

    The strategies utilized to effectively perform a given task change with practice and experience. During a spatial navigation task, with relatively little training, performance is typically attentive enabling an individual to locate the position of a goal by relying on spatial landmarks. These (place) strategies require an intact hippocampus. With task repetition, performance becomes automatic; the same goal is reached using a fixed response or sequence of actions. These (response) strategies require an intact striatum. The current work aims to understand the activation patterns across these neural structures during this experience-dependent strategy transition. This was accomplished by region-specific measurement of activity-dependent immediate early gene expression among rats trained to different degrees on a dual-solution task (i.e., a task that can be solved using either place or response navigation). As expected, rats increased their reliance on response navigation with extended task experience. In addition, dorsal hippocampal expression of the immediate early gene Arc was considerably reduced in rats that used a response strategy late in training (as compared with hippocampal expression in rats that used a place strategy early in training). In line with these data, vicarious trial and error, a behavior linked to hippocampal function, also decreased with task repetition. Although Arc mRNA expression in dorsal medial or lateral striatum alone did not correlate with training stage, the ratio of expression in the medial striatum to that in the lateral striatum was relatively high among rats that used a place strategy early in training as compared with the ratio among over-trained response rats. Altogether, these results identify specific changes in the activation of dissociated neural systems that may underlie the experience-dependent emergence of response-based automatic navigation. PMID:26976088

  16. A multivariate surface-based analysis of the putamen in premature newborns: regional differences within the ventral striatum.

    Directory of Open Access Journals (Sweden)

    Jie Shi

    Full Text Available Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity

  17. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Directory of Open Access Journals (Sweden)

    Makoto Ito

    2015-11-01

    Full Text Available Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS, the dorsomedial striatum (DMS, and the ventral striatum (VS identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  18. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    OpenAIRE

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly...

  19. Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

    Science.gov (United States)

    Ito, Makoto; Doya, Kenji

    2015-11-01

    Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS), the dorsomedial striatum (DMS), and the ventral striatum (VS) identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

  20. Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

    OpenAIRE

    Hiroaki Kawamichi; Hiroaki Kawamichi; Hiroaki Kawamichi; Sho K Sugawara; Yuki H Hamano; Yuki H Hamano; Kai Makita; Masahiro Matsunaga; Hiroki C Tanabe; Yuichi Ogino; Shigeru Saito; Norihiro Sadato; Norihiro Sadato

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  1. Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

    OpenAIRE

    Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

    2016-01-01

    Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

  2. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  3. Prenatal ethanol exposure alters synaptic plasticity in the dorsolateral striatum of rat offspring via changing the reactivity of dopamine receptor.

    Directory of Open Access Journals (Sweden)

    Rong Zhou

    Full Text Available Prenatal exposure to high-level ethanol (EtOH has been reported to produce hyperlocomotion in offspring. Previous studies have demonstrated synaptic plasticity in cortical afferent to the dorsolateral (DL striatum is involved in the pathogensis of hyperlocomotion. Here, prenatal EtOH-exposed rat offspring were used to investigate whether maternal EtOH exposure affected synaptic plasticity in the DL striatum. We found high-frequency stimulation (HFS induced a weaker long-term potentiation (LTP in EtOH rats than that in control rats at postnatal day (PD 15. The same protocol of HFS induced long-term depression (LTD in control group but still LTP in EtOH group at PD 30 or PD 40. Furthermore, enhancement of basal synaptic transmission accompanied by the decrease of pair-pulse facilitation (PPF was observed in PD 30 EtOH offspring. The perfusion with D1-type receptors (D1R antagonist SCH23390 recovered synaptic transmission and blocked the induction of abnormal LTP in PD 30 EtOH offspring. The perfusion with D2-type receptors (D2R agonist quinpirole reversed EtOH-induced LTP into D1R- and metabotropic glutamate receptor-dependent LTD. The data provide the functional evidence that prenatal ethanol exposure led to the persistent abnormal synaptic plasticity in the DL striatum via disturbing the balance between D1R and D2R.

  4. Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

    Science.gov (United States)

    Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

    2017-11-01

    Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

  5. Segmentation of the Striatum from MR Brain Images to Calculate the -TRODAT-1 Binding Ratio in SPECT Images

    Directory of Open Access Journals (Sweden)

    Ching-Fen Jiang

    2013-01-01

    Full Text Available Quantification of regional -TRODAT-1 binding ratio in the striatum regions in SPECT images is essential for differential diagnosis between Alzheimer's and Parkinson's diseases. Defining the region of the striatum in the SPECT image is the first step toward success in the quantification of the TRODAT-1 binding ratio. However, because SPECT images reveal insufficient information regarding the anatomical structure of the brain, correct delineation of the striatum directly from the SPECT image is almost impossible. We present a method integrating the active contour model and the hybrid registration technique to extract regions from MR T1-weighted images and map them into the corresponding SPECT images. Results from three normal subjects suggest that the segmentation accuracy using the proposed method was compatible with the expert decision but has a higher efficiency and reproducibility than manual delineation. The binding ratio derived by this method correlated well (R2 = 0.76 with those values calculated by commercial software, suggesting the feasibility of the proposed method.

  6. A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand

    International Nuclear Information System (INIS)

    Ishikawa, Nobuyoshi; Nakamura, Toshihiko; Satou, Motohiro; Takeda, Tohoru; Wu, Jin; Motoji, Naomi; Shigematsu, Akiyo.

    1995-01-01

    Iodo-125-labeled iodobenzamide ([ 125 I]IBZM) is used as a specific binding radioligand to dopamine D 2 receptors with high affinity and selectivity. The radioligand was homogeneously distributed in the whole brain initially after anministration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D 2 receptors in the living brain. (author)

  7. Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

    Science.gov (United States)

    Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

    2009-01-01

    Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

  8. Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

    Science.gov (United States)

    Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

    2009-02-11

    Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

  9. Analysis of the Substantia Innominata Volume in Patients with Parkinson’s Disease with Dementia, Dementia with Lewy Bodies, and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Hee Jin Kim

    2011-10-01

    Full Text Available Background and Purpose The substantia innominata (SI contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. Methods We used magnetic resonance imaging (MRI-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI, Alzheimer’s disease (AD, Parkinson’s disease-mild cognitive impairment (PD-MCI, PD with dementia (PDD, dementia with Lewy bodies (DLB, and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE, was examined. Results Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029 and DLB (p = 0.011 compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB, there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001, whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD. Conclusions Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy.

  10. Methyllycaconitine prevents methamphetamine-induced effects in mouse striatum: involvement of alpha7 nicotinic receptors.

    Science.gov (United States)

    Escubedo, Elena; Chipana, Carlos; Pérez-Sánchez, Mónica; Camarasa, Jordi; Pubill, David

    2005-11-01

    In a previous study, we demonstrated that in rat striatal synaptosomes, methamphetamine (METH)-induced reactive oxygen species (ROS) production was prevented by methyllycaconitine (MLA), a specific antagonist of alpha7 neuronal nicotinic acetylcholine receptors (alpha7 nAChR). The aim of this study was to test the influence of MLA on acute METH effects and neurotoxicity in mice, using both in vivo and in vitro models. MLA inhibited METH-induced climbing behavior by 50%. Acute effects after 30-min preincubation with 1 microM METH also included a decrease in striatal synaptosome dopamine (DA) uptake, which was prevented by MLA. METH-induced neurotoxicity was assessed in vivo in terms of loss of striatal dopaminergic terminals (73%) and of tyrosine hydroxylase levels (by 90%) at 72 h post-treatment, which was significantly attenuated by MLA. Microglial activation [measured as 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide binding] was also present at 24 h post-treatment and was fully prevented by MLA, tending to confirm its neuroprotective activity. MLA had no effect on METH-induced hyperthermia. Additionally, flow cytometry assays showed that METH-induced ROS generation occurs inside synaptosomes from mouse striatum. This effect implied release of vesicular DA and was calcium-, neuronal nitric-oxide synthase-, and protein kinase C-dependent. MLA and alpha-bungarotoxin, but not dihydro-beta-erythroidine (an antagonist that blocks nAChR-containing beta2 subunits), fully prevented METH-induced ROS production without affecting vesicular DA uptake. The importance of this study lies not only in the neuroprotective effect elicited by the blockade of the alpha7 nicotinic receptors by MLA but also in that it proposes a new mechanism with which to study METH-induced acute and long-term effects.

  11. Enhancing and impairing extinction of habit memory through modulation of NMDA receptors in the dorsolateral striatum.

    Science.gov (United States)

    Goodman, Jarid; Ressler, Reed L; Packard, Mark G

    2017-06-03

    The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder). Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Stress-related anhedonia is associated with ventral striatum reactivity to reward and transdiagnostic psychiatric symptomatology

    Science.gov (United States)

    Corral-Frías, Nadia S.; Nikolova, Yuliya S.; Michalski, Lindsay J.; Baranger, David A.A.; Hariri, Ahmad R.; Bogdan, Ryan

    2015-01-01

    Background Early life stress (ELS) is consistently associated with increased risk for subsequent psychopathology. Individual differences in neural response to reward may confer vulnerability to stress-related psychopathology. Using data from the ongoing Duke Neurogenetics Study, the present study examined whether reward-related ventral striatum (VS) reactivity moderates the relationship between retrospectively reported ELS and anhedonic symptomatology. We further assessed whether individual differences in reward-related VS reactivity were associated with other depressive symptoms and problematic alcohol use via stress-related anhedonic symptoms and substance use-associated coping. Method Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) was collected while participants (n = 906) completed a card-guessing task, which robustly elicits VS rea