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Sample records for acid-induced hippocampal degeneration

  1. Wnt/β-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy.

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    Qu, Zhengyi; Su, Fang; Qi, Xueting; Sun, Jianbo; Wang, Hongcai; Qiao, Zhenkui; Zhao, Hong; Zhu, Yulan

    2017-10-01

    Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid-induced rat epilepsy model to investigate whether Wnt/β-catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy. Immunostaining and western blotting results showed that the expression levels of β-catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway, were up-regulated during acute epilepsy induced by the injection of kainic acids, indicating that Wnt signalling pathway was activated in kainic acid-induced temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of the Wnt signalling by knocking down β-catenin attenuated aberrant neurogenesis induced by kainic acids injection. Altogether, Wnt/β-catenin signalling pathway mediated hippocampal neurogenesis during epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the epileptogenesis process of temporal lobe epilepsy. In the present study, we discovered that Wnt3a/β-catenin signalling pathway serves as a link between aberrant neurogenesis and underlying remodelling in the hippocampus, leading to temporal lobe epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Study on protective effect of ketogenic diet against hippocampal neurons of kainic acid-induced epileptic rats

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    Nan-nan ZHANG

    2015-11-01

    neurons of kainic acid-induced epileptic rats. DOI: 10.3969/j.issn.1672-6731.2015.11.011

  3. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

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    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus).

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    Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M D; Van Bonn, William

    2014-05-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. Copyright © 2013 Wiley Periodicals, Inc.

  5. Sub-regional hippocampal injury is associated with fornix degeneration in Alzheimer's disease

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    Dong Young Lee

    2012-04-01

    Full Text Available We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer’s disease (AD through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI, was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI, and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA, was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.

  6. Sub-Regional Hippocampal Injury is Associated with Fornix Degeneration in Alzheimer’s Disease

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    Lee, Dong Young; Fletcher, Evan; Carmichael, Owen Thomas; Singh, Baljeet; Mungas, Dan; Reed, Bruce; Martinez, Oliver; Buonocore, Michael H.; Persianinova, Maria; DeCarli, Charles

    2012-01-01

    We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer’s disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury. PMID:22514534

  7. Acupuncture inhibits kainic Acid-induced hippocampal cell death in mice.

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    Kim, Seung-Tae; Jeon, Songhee; Park, Hae Jeong; Hong, Mee-Sook; Jeong, Wu Byung; Kim, Jang-Hyun; Kim, Yeonjung; Lee, Hye-Jung; Park, Hi-Joon; Chung, Joo-Ho

    2008-02-01

    We examined whether acupuncture can reduce both the incidence of seizures and hippocampal cell death using a mouse model of kainic acid (KA)-induced epilepsy. ICR mice were given acupuncture once a day at acupoint HT8 (sobu) bilaterally during 2 days before KA injection. After an intracerebroventricular injection of 0.1 microg of KA, acupuncture treatment was subsequently administered once more (total 3 times), and the degree of seizure was observed for 20 min. Three hours after injection, the survival of neuronal cells and the expressions of c-Fos, c-Jun, and glutamate decarboxylase (GAD)-67 in the CA1 and CA3 were determined using immunohistochemistry and Western blotting techniques. Acupuncture reduced the severity of the KA-induced epileptic seizure and the rate of neural cell death, and it also decreased the expressions of c-Fos and c-Jun induced by KA in the hippocampus. Furthermore, acupuncture increased GAD-67 expressions in the same areas. These results demonstrated that it could inhibit the KA-induced epileptic seizure and hippocampal cell death by increasing GAD-67 expressions.

  8. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

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    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to p...

  9. Hippocampal sclerosis dementia: An amnesic variant of frontotemporal degeneration

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    Chiadi U. Onyike

    Full Text Available ABSTRACT Objective: To describe characteristics of hippocampal sclerosis dementia. Methods: Convenience sample of Hippocampal sclerosis dementia (HSD recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. Results: The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2% had amnesia at illness onset, and many (54.2% showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD was uncommon (seen in 8%. Conclusion: HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant.

  10. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

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    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia...... periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  11. Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus.

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    Xiang Gao

    Full Text Available Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI. Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared. Less research has been focused on these spared neurons, which may also be injured or compromised by TBI. Here we examined the dendrite morphologies, dendritic spines, and synaptic structures using a genetic approach in combination with immunohistochemistry and Golgi staining. We found that although most of the mature granular neurons were spared following TBI at a moderate level of impact, they exhibited dramatic dendritic beading and fragmentation, decreased number of dendritic branches, and a lower density of dendritic spines, particularly the mushroom-shaped mature spines. Further studies showed that the density of synapses in the molecular layer of the hippocampal dentate gyrus was significantly reduced. The electrophysiological activity of neurons was impaired as well. These results indicate that TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration in pathohistology. TBI also impairs the function of the spared mature granular neurons in the hippocampal dentate gyrus. These observations point to a potential anatomic substrate to explain, in part, the development of posttraumatic memory deficits. They also indicate that dendritic damage in the hippocampal dentate gyrus may serve as a therapeutic target following TBI.

  12. Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory.

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    Ladrón de Guevara-Miranda, David; Moreno-Fernández, Román Darío; Gil-Rodríguez, Sara; Rosell-Valle, Cristina; Estivill-Torrús, Guillermo; Serrano, Antonia; Pavón, Francisco J; Rodríguez de Fonseca, Fernando; Santín, Luis J; Castilla-Ortega, Estela

    2018-02-26

    Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA 1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA-treated mice exhibited reduced long-term CPP retention and an approximately twofold increase in the number of adult-born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425-treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety-like responses. In a second experiment, normal and LPA 1 -receptor-deficient mice were acutely infused with LPA, which revealed that LPA 1 -mediated signaling was required for LPA-induced proliferative actions. These results suggest that the LPA/LPA 1 pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro-AHN strategies to treat aberrant cognition in those addicted to cocaine. © 2018 Society for the Study of Addiction.

  13. Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

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    Bae Hwan Lee

    2013-09-01

    Full Text Available Vitamin E, such as alpha-tocopherol (ATPH and alpha-tocotrienol (ATTN, is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 µM treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 µM or ATTN (100 µM significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF fluorescence and levels of thiobarbiturate reactive substances (TBARS were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment.

  14. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

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    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory......, respectively. Conversely, there was no deterioration of cognitive functioning in sham lesioned Tg2576 mice or wild type littermates (wt) receiving the immunotoxin. At 10 months of age, release of acetylcholine (ACh) was addressed by microdialysis in conscious mice. Scopolamine-induced increases in hippocampal...... ACh efflux was significantly reduced in SAP lesioned Tg2576 mice compared to sham lesioned Tg2576 mice. Intriguingly, there was no significant difference in ACh efflux between wt treatment groups. Following SAP treatment, choline acetyltransferase activity was reduced in the hippocampus and frontal...

  15. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

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    Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas; Schreckenberger, Matthias; Cumming, Paul; Stoeter, Peter; Gerhard, Alex

    2011-01-01

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  16. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

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    Chung-Hsiang Liu

    2012-01-01

    Full Text Available Uncaria rhynchophylla (UR, which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA- induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

  17. Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation

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    Quirion, R.; Chabot, J.-G.; Dore, S.; Seto, D.; Kar, S.

    1997-01-01

    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [ 125 I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [ 125 I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [ 125 I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [ 125 I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [ 125 I]insulin receptor binding was noted at all time points in the molecular layer of the

  18. Electroacupuncture at ST36-ST37 and at Ear Ameliorates Hippocampal Mossy Fiber Sprouting in Kainic Acid-Induced Epileptic Seizure Rats

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    Chung-Hsiang Liu

    2014-01-01

    Full Text Available Our previous study showed that mossy fiber sprouting can occur in the hippocampus region in rats 6 wk after kainic acid-induced epileptic seizure, and this mossy fiber sprouting can facilitate epileptogenesis. Transcutaneous auricular vagal nerve stimulation (VNS, which is similar to cervical VNS, can reduce the occurrence of epileptic seizure in intractable epilepsy patients. Greater parasympathetic nerve activity can be caused by 2 Hz electroacupuncture (EA. Therefore, we investigated the effect of 2 Hz EA at ST-36-ST37 and at the ear on mossy fiber sprouting in kainic-treated Sprague-Dawley rats. The results indicated that applying 2 Hz EA at ST36-ST37 and at the ear for 3 d per week over 6 consecutive weeks can ameliorate mossy fiber sprouting in the hippocampus region of rats. These results indicated that applying 2 Hz EA at ST36-ST37 and at the ear might be beneficial for the treatment and prevention of epilepsy in humans.

  19. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

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    Wei Jiang

    Full Text Available Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD. Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons. We found that Okadaic acid (OA induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH, superoxide dismutase (SOD, mitochondria membrane potential (MMP and Glutathione peroxidase (GSH-Px. It up-regulated malondialdehyde (MDA production and intracellular reactive oxygen species (ROS. In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β and mitogen activated protein kinase (MAPK were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.

  20. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

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    Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); Schreckenberger, Matthias [University Medical Center Mainz, Department of Nuclear Medicine, Mainz (Germany); Cumming, Paul [University of Munich, Department of Nuclear Medicine, Munich (Germany); Stoeter, Peter [University Medical Center Mainz, Institute of Neuroradiology, Mainz (Germany); Gerhard, Alex [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom)

    2011-12-15

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 {+-} 1.7) were studied with [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  1. Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration.

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    Brenowitz, Willa D; Monsell, Sarah E; Schmitt, Frederick A; Kukull, Walter A; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively "pure" HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials.

  2. 3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital.

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    Nomura, Shohei; Shimakawa, Shuichi; Miyamoto, Ryohei; Fukui, Miho; Tamai, Hiroshi

    2014-11-24

    There is accumulating evidence that reactive oxygen species are involved in the development of seizures under pathological conditions, and antioxidant treatments are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of induced seizures has been widely used to study temporal lobe epilepsy. However, research on the use of free radical scavengers following KA-induced status epilepticus (SE) is limited. We examined whether antioxidants already used in humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the acquisition of hyperexcitability when administered as a single dose after SE. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N-acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined the threshold for seizures induced by inhalation of flurothyl ether 12 weeks after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We found that edaravone or NAC prevented neuronal cell loss and mossy fiber sprouting, and increased the threshold for seizures induced by flurothyl ether, even when administered after KA-induced SE. These results demonstrate that a single dose of edaravone or NAC can protect against neuronal cell loss and epileptogenesis when administered after SE ceased by pentobarbital. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

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    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  4. Hippocampal P3-Like Auditory Event-Related Potentials are Disrupted in a Rat Model of Cholinergic Degeneration in Alzheimer's Disease: Reversal by Donepezil Treatment

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe

    2014-01-01

    P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related......-treatment with 1 mg/kg donepezil. Infusion of SAP reduced the hippocampal choline acetyltransferase activity by 75%. Behaviorally defined cognitive performance was comparable between treatment groups. The present study suggests that AD-like deficits in P3-like ERPs may be mimicked by the basal forebrain...

  5. The role of rosemary extract in degeneration of hippocampal neurons induced by kainic acid in the rat: A behavioral and histochemical approach.

    Science.gov (United States)

    Naderali, Elahe; Nikbakht, Farnaz; Ofogh, Sattar Norouzi; Rasoolijazi, Homa

    2018-01-01

    Systemic Kainic Acid (KA) administration has been used to induce experimental temporal lobe epilepsy in rats. The aim of this study was to evaluate the neuroprotective effect of rosemary extract (RE, 40% Carnosic acid) against KA-induced neurotoxicity in hippocampus and impaired learning and memory. Animals received a single dose of KA (9.5 mg/kg) intraperitoneally (i.p.) (KA group) and were observed for 2 h and were scored from 0 (for normal, no convulsion) to 5 (for continuous generalized limbic seizures). RE (100 mg/kg, orally) was administered daily for 23 days, starting a week before KA injection (KA+RE group). Neuronal degeneration in hippocampus was demonstrated by using Fluoro-Jade B immunofluorescence. The number of pyramidal cells in hippocampus was evaluated by Nissl staining. Also, the Morris Water Maze and Shuttle box have been used to assess spatial memory and passive avoidance learning, respectively. Our results revealed that, after treatment with RE, neuronal loss in CA1 decreased significantly in the animals in KA+RE group. The Morris water navigation task results revealed that spatial memory impairment decreased in the animals in KA+RE group. Furthermore, results in Shuttle box test showed that passive avoidance learning impairment significantly, upgraded in the animals in KA+RE group. These results suggest that RE may improve the spatial and working memory deficits and also neuronal degeneration induced by toxicity of KA in the rat hippocampus, due to its antioxidant activities.

  6. Striatonigral Degeneration

    Science.gov (United States)

    ... See More About Research The NINDS supports and conducts research on disorders of the brain and nervous system such as striatonigral degeneration. This research ... Publications Definition Striatonigral ...

  7. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice......, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...

  8. Hepatocerebral degeneration

    Science.gov (United States)

    Hepatocerebral degeneration is a brain disorder that occurs in people with liver damage. ... This condition may occur in any case of acquired liver failure, ... can damage brain tissue. Specific areas of the brain, such as ...

  9. Acupuncture suppresses kainic acid-induced neuronal death and inflammatory events in mouse hippocampus.

    Science.gov (United States)

    Kim, Seung-Tae; Doo, Ah-Reum; Kim, Seung-Nam; Kim, Song-Yi; Kim, Yoon Young; Kim, Jang-Hyun; Lee, Hyejung; Yin, Chang Shik; Park, Hi-Joon

    2012-09-01

    The administration of kainic acid (KA) causes seizures and produces neurodegeneration in hippocampal CA3 pyramidal cells. The present study investigated a possible role of acupuncture in reducing hippocampal cell death and inflammatory events, using a mouse model of kainic acid-induced epilepsy. Male C57BL/6 mice received acupuncture treatments at acupoint HT8 or in the tail area bilaterally once a day for 2 days and again immediately after an intraperitoneal injection of KA (30 mg/kg). HT8 is located on the palmar surface of the forelimbs, between the fourth and fifth metacarpal bones. Twenty-four hours after the KA injection, neuronal cell survival, the activations of microglia and astrocytes, and mRNA expression of two proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were measured in the hippocampus. Acupuncture stimulation at HT8, but not in the tail area, significantly reduced the KA-induced seizure, neuron death, microglial and astrocyte activations, and IL-1β mRNA expression in the hippocampus. The acupuncture stimulation also decreased the mRNA expression of TNF-α, but it was not significant. These results indicate that acupuncture at HT8 can inhibit hippocampal cell death and suppress KA-induced inflammatory events, suggesting a possible role for acupuncture in the treatment of epilepsy.

  10. Hippocampal Disconnection in Early Alzheimer's Disease : A 7 Tesla MRI Study

    NARCIS (Netherlands)

    Wisse, Laura E. M.; Reijmer, Yael D.; ter Telgte, Annemieke; Kuijf, Hugo J.; Leemans, Alexander; Luijten, Peter R.; Koek, Huiberdina L.; Geerlings, Mirjam I.; Biessels, Geert Jan

    2015-01-01

    Background: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. Objective: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and

  11. Hippocampal disconnection in early Alzheimer's disease: a 7 tesla MRI study

    NARCIS (Netherlands)

    Wisse, L.E.; Reijmer, Y.D.; Telgte, A. ter; Kuijf, H.J.; Leemans, A.; Luijten, P.R.; Koek, H.L.; Geerlings, M.I.; Biessels, G.J.

    2015-01-01

    BACKGROUND: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. OBJECTIVE: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and

  12. Macular degeneration (image)

    Science.gov (United States)

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  13. American Macular Degeneration Foundation

    Science.gov (United States)

    ... Policy Disclaimer Contact Us Donate Store The American Macular Degeneration Foundation The American Macular Degeneration Foundation (AMDF) is ... Ed Asner Video Clip An Inspiring Her-story Macular Degeneration is the leading cause of vision loss, affecting ...

  14. Degenerate Euler zeta function

    OpenAIRE

    Kim, Taekyun

    2015-01-01

    Recently, T. Kim considered Euler zeta function which interpolates Euler polynomials at negative integer (see [3]). In this paper, we study degenerate Euler zeta function which is holomorphic function on complex s-plane associated with degenerate Euler polynomials at negative integers.

  15. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina

    2006-01-01

    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  16. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  17. Degenerate Gauss hypergeometric functions

    OpenAIRE

    Vidunas, Raimundas

    2004-01-01

    This is a study of terminating and ill-defined Gauss hypergeometric functions. Corresponding hypergeometric equations have a degenerate set of of 24 Kummer's solutions. We describe those solutions and relations between them.

  18. Selective amygdalohippocampectomy for hippocampal sclerosis: postoperative MR appearance.

    Science.gov (United States)

    Renowden, S A; Matkovic, Z; Adams, C B; Carpenter, K; Oxbury, S; Molyneux, A J; Anslow, P; Oxbury, J

    1995-10-01

    To analyze the anatomic consequences of selective amygdalohippocampectomy (AH) in patients with hippocampal sclerosis and to correlate the clinical outcome with the MR appearance. Seventeen patients were examined with clinical and neuropsychologic examination and cranial MR after AH (7 transcortical AH, 10 trans-Sylvian AH). The clinical and neuropsychologic outcomes after AH were compared with those of anterior lobectomy (ATL). There was no significant difference in seizure cure between transcortical or trans-Sylvian AH and ATL. However, patients with left AH fared significantly better in terms of verbal IQ and nonverbal memory when compared with those with left ATL. Verbal memory and cognition were not significantly different in the two AH groups. Variable amounts of hippocampal and amygdala remnants were found in both AH groups and did not correlate with seizure cure. White matter change consistent with gliosis probably secondary to wallerian degeneration was demonstrated in the anterior temporal lobe to a mean distance of 4.5 cm after transcortical AH and to a lesser degree as a consequence of trans-Sylvian AH. Nine patients (53%) (4 transcortical All, 5 trans-Sylvian AH) demonstrated wallerian degeneration in the optic radiations after surgery. All had incomplete contralateral quadrantanopia. There is more secondary damage to the temporal lobe after AH than was previously recognized. The extent of hippocampal and amygdala resection in AH do not seem to be directly related to seizure cure. Visual field defects are common in AH because of the anterior but variable course of the optic radiations

  19. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  20. Kraepelin and degeneration theory.

    Science.gov (United States)

    Hoff, Paul

    2008-06-01

    Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy.

  1. Increased isoprostane levels in oleic acid-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Koichi [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Koizumi, Tomonobu, E-mail: tomonobu@shinshu-u.ac.jp [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Nakagawa, Rikimaru [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Obata, Toru [Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo (Japan)

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  2. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert

    2003-01-01

    The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3...... weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated...... the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice...

  3. Beneficial effect of rice bran extract against 3-nitropropionic acid induced experimental Huntington's disease in rats

    Directory of Open Access Journals (Sweden)

    Navneet Kaur

    2015-01-01

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, characterized by progressive motor and non-motor dysfunction due to degeneration of medium spiny neurons in striatum. 3-Nitropropionic acid is commonly used to induce the animal model of HD. Rice bran is supposed to have beneficial effects on mitochondrial function. The present study has been designed to explore the effect of rice bran extract against 3-Nitropropionic acid induced neurotoxicity in rats. 3-Nitropropionic acid (10 mg/kg, i.p was administered systemically for 21 days. Hexane and ethanol extract of rice bran were prepared using Soxhlation. Hexane (250 mg/kg and ethanol extract (250 mg/kg were administered per os for 21 days in 3-NP treated groups. Behavioral parameters (body weight, grip strength, motor coordination, locomotion were conducted on 7th, 14th and 21st day. Animals were sacrificed on 22nd day for biochemical, mitochondrial dysfunction (Complex II, neuroinflammatory and neurochemical estimation in striatum. This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration and decreased glutathione, mitochondrial function (decreased Complex II enzyme activity, pro-inflammatory mediators and neurochemical levels in 3-nitropropionic acid treated animals. Administration of hexane and ethanol extract prevented the behavioral, biochemical, neuroinflammatory (increased TNF-α, IL-1β and IL-6 and neurochemical alterations (decreased dopamine, norepinephrine, serotonin, 5-hydroxy indole acetic acid, GABA and increased 3,4-dihydro phenyl acetaldehyde, homovanillic acid and glutamate levels induced by 3-nitropropionic acid. The outcomes of present study suggest that rice bran extract is beneficial and might emerge as an adjuvant or prophylactic therapy for treatment of HD like symptoms.

  4. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...... and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...

  5. MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

    Science.gov (United States)

    Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

    2016-03-01

    In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

  6. Adjacent segment degeneration

    OpenAIRE

    Birjandi, Alireza

    2012-01-01

    Abstract: Adjacent segment disease (ASD) is defined as degeneration that develops at mobile segments above or below a fused spinal segment and usually develops after spinal fusion or other back surgeries. Nearly 5 decades ago, the medical findings related to ASD were usually released in case reports as a relatively unusual complication of lumbar or lumbosacral fusions. Since the initial reports, ASD has been found to occur more often than the earlier predictions for its prospect incidence. It...

  7. Structure and rheological properties of acid-induced egg white protein gels

    NARCIS (Netherlands)

    Weijers, M.; Velde, F. van de; Stijnman, A.; Pijpekamp, A. van de; Visschers, R.W.

    2006-01-01

    This study compares the rheological properties of acid-induced gels prepared of industrial spray-dried egg white proteins (EWP) with the acid-induced gels prepared of ovalbumin (OA) and whey protein isolate (WPI). Also we aimed to form transparent gels of EWP by means of the cold-gelation process.

  8. Caffeic Acid Induces Apoptosis in Human Cervical Cancer Cells Through the Mitochondrial Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Chun Chang

    2010-12-01

    Conclusion: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

  9. White matter disruption at the prodromal stage of Alzheimer's disease: Relationships with hippocampal atrophy and episodic memory performance

    Directory of Open Access Journals (Sweden)

    Florence Rémy

    2015-01-01

    Full Text Available White matter tract alterations have been consistently described in Alzheimer's disease (AD. In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011 (n = 22 and healthy controls (n = 15. Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA and increase of radial diffusivity (RD in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

  10. Possible Role of the Glycogen Synthase Kinase-3 Signaling Pathway in Trimethyltin-Induced Hippocampal Neurodegeneration in Mice

    Science.gov (United States)

    Kim, Sung-Ho; Kim, Jong-Choon; Wang, Hongbing; Shin, Taekyun; Moon, Changjong

    2013-01-01

    Trimethyltin (TMT) is an organotin compound with potent neurotoxic effects characterized by neuronal destruction in selective regions, including the hippocampus. Glycogen synthase kinase-3 (GSK-3) regulates many cellular processes, and is implicated in several neurodegenerative disorders. In this study, we evaluated the therapeutic effect of lithium, a selective GSK-3 inhibitor, on the hippocampus of adult C57BL/6 mice with TMT treatment (2.6 mg/kg, intraperitoneal [i.p.]) and on cultured hippocampal neurons (12 days in vitro) with TMT treatment (5 µM). Lithium (50 mg/kg, i.p., 0 and 24 h after TMT injection) significantly attenuated TMT-induced hippocampal cell degeneration, seizure, and memory deficits in mice. In cultured hippocampal neurons, lithium treatment (0–10 mM; 1 h before TMT application) significantly reduced TMT-induced cytotoxicity in a dose-dependent manner. Additionally, the dynamic changes in GSK-3/β-catenin signaling were observed in the mouse hippocampus and cultured hippocampal neurons after TMT treatment with or without lithium. Therefore, lithium inhibited the detrimental effects of TMT on the hippocampal neurons in vivo and in vitro, suggesting involvement of the GSK-3/β-catenin signaling pathway in TMT-induced hippocampal cell degeneration and dysfunction. PMID:23940567

  11. Protective effect of carvacrol on acetic acid-induced colitis.

    Science.gov (United States)

    de Santana Souza, Marilia Trindade; Teixeira, Daiane Franco; de Oliveira, Janaíne Prata; Oliveira, Alan Santos; Quintans-Júnior, Lucindo José; Correa, Cristiane Bani; Camargo, Enilton Aparecido

    2017-12-01

    The pharmacological therapy for inflammatory bowel diseases continues to be problematic, and requires new alternative options. In this study, we tested the hypothesis that carvacrol (CAR), a phenolic monoterpene with anti-inflammatory and antioxidant activities, can treat experimental colitis in mice. C57BL/6 mice (n=8/group) were subjected to intrarectal administration of acetic acid (5%) to induce colitis. Mice were pretreated with CAR (25, 50 or 100mg/kg, p.o.) every 12h for three days prior to the induction. Abdominal hyperalgesia, macroscopic and microscopic colon damage, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, oxidative stress markers, and antioxidant enzyme activities were evaluated. Pretreatment with all doses of CAR significantly decreased abdominal hyperalgesia and colon MPO activity and TNF-α and IL-1β levels. A reduction in macroscopic and microscopic damage (p<0.05) was observed at doses of 50 and 100mg/kg CAR. Pretreatment with CAR significantly reduced lipid peroxidation (for all doses) and increased sulfhydryl groups (at 100mg/kg). This effect was accompanied by a significant increase in catalase, superoxide dismutase, and glutathione peroxidase activities. These findings indicate that CAR protected mice from acetic acid-induced colitis by reducing inflammatory, nociceptive, and oxidative damages. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  13. Metformin Protects Rat Hepatocytes against Bile Acid-Induced Apoptosis

    Science.gov (United States)

    Woudenberg-Vrenken, Titia E.; Conde de la Rosa, Laura; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han

    2013-01-01

    Background Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD). Metformin activates AMP-activated protein kinase (AMPK), the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR). Both AMPK and mTOR are able to modulate cell death. Aim To evaluate the effects of metformin on hepatocyte cell death. Methods Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA) or TNFα in combination with actinomycin D (actD). AMPK, mTOR and phosphoinositide-3 kinase (PI3K)/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. Results Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. Conclusion Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation. PMID:23951244

  14. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...

  15. Mechanism of acid-induced folding of proteins.

    Science.gov (United States)

    Goto, Y; Takahashi, N; Fink, A L

    1990-04-10

    We have previously shown [Goto, Y., Calciano, L. J., & Fink, A. L. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 573-577] that beta-lactamase, cytochrome c, and apomyoglobin are maximally unfolded at pH 2 under conditions of low ionic strength, but a further decrease in pH, by increasing the concentration of HCl, refolds the proteins to the A state with properties similar to those of a molten globule state. To understand the mechanism of acid-induced refolding of protein structure, we studied the effects of various strong acids and their neutral salts on the acid-unfolded states of ferricytochrome c and apomyoglobin. The conformational transition of cytochrome c was monitored at 20 degrees C by using changes in the far-UV CD and in the Soret absorption at 394 nm, and that of apomyoglobin was monitored by changes in the far-UV CD. Various strong acids (i.e., sulfuric acid, perchloric acid, nitric acid, trichloroacetic acid, and trifluoroacetic acid) refolded the acid-unfolded cytochrome c and apomyoglobin to the A states as was the case with HCl. For both proteins neutral salts of these acids caused similar conformational transitions, confirming that the anions are responsible for bringing about the transition. The order of effectiveness of anions was shown to be ferricyanide greater than ferrocyanide greater than sulfate greater than thiocyanate greater than perchlorate greater than iodide greater than nitrate greater than trifluoroacetate greater than bromide greater than chloride.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on Hippocampal Neurons in Epileptic Monkeys.

    Science.gov (United States)

    Yang, An-Chao; Shi, Lin; Li, Lu-Ming; Li, Jun-Ju; Jiang, Yin; Meng, Da-Wei; Zhu, Guan-Yu; Chen, Ying-Chuan; Lu, De-Hong; Zhang, Jian-Guo

    2015-01-01

    Stimulation of the anterior nucleus of the thalamus (ANT) is effective in seizure reduction, but the mechanisms underlying the beneficial effects of ANT stimulation are unclear. To assess the beneficial effects of ANT stimulation on hippocampal neurons of epileptic monkeys. Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys. Behavioral seizures were continuously monitored. Immunohistochemical staining and western blot assays were performed to assess the hippocampal injury and the effects of ANT stimulation. The frequency of seizures was 42.8% lower in the stimulation group compared with the sham-stimulation group. Immunohistochemical staining and western blot analyses indicated that neuronal loss and apoptosis were less severe and that neurofilament synthesis was enhanced in the stimulation monkeys compared with the sham-stimulation group. These data showed that the hippocampal injury was less severe in monkeys in the stimulation group than in those in the sham-stimulation group. Our data suggest that chronic ANT stimulation may exert protective effects on hippocampal neurons and boost the regeneration of neuronal fibers. These effects may be closely related to the mechanisms of ANT stimulation in epilepsy treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age

    OpenAIRE

    Hattiangady, Bharathi; Rao, Muddanna S.; Shetty, Ashok K.

    2008-01-01

    A remarkable up-regulation of neurogenesis through increased proliferation of neural stem/progenitor cells (NSCs) is a well-known plasticity displayed by the young dentate gyrus (DG) following brain injury. To ascertain whether this plasticity is preserved during aging, we quantified DG neurogenesis in the young adult, middle-aged and aged F344 rats after kainic acid induced hippocampal injury. Measurement of new cells that are added to the dentate granule cell layer (GCL) between post-injury...

  18. Update on Hippocampal Sclerosis.

    Science.gov (United States)

    Dutra, Juliana R; Cortés, Etty P; Vonsattel, Jean Paul G

    2015-10-01

    The diagnostic hallmarks of hippocampal sclerosis (HS) are severe volume loss of the hippocampus, severe neuronal loss, and reactive gliosis involving primarily two especially vulnerable fields, CA1 and the subiculum. Occasionally, HS may be the only neuropathological change detected in older individuals with dementia and is known as pure HS. In the majority of cases, HS occurs in the setting of other degenerative changes, usually Alzheimer's disease (AD). In these cases, it is classified as combined HS. Although a clinical profile for HS has been identified, its similarities with AD make the diagnosis during life quite challenging; thus, the diagnosis is often made postmortem. The pathogenesis of HS is not completely understood, but the strong association with transactive response DNA-binding protein 43 (TDP-43), in approximately 90%, and the recent discovery of genetic risk factors are important contributions to a better understanding of the disease process.

  19. Second order degenerate elliptic equations

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1988-08-01

    Using an improved Sobolev inequality we study a class of elliptic operators which is degenerate inside the domain and strongly degenerate near the boundary of the domain. Our results are applicable to the L 2 -boundary value problem and the mixed boundary problem. (author). 18 refs

  20. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  1. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, N.|info:eu-repo/dai/nl/314418059

    2011-01-01

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  2. Stress, depression and hippocampal damage

    Indian Academy of Sciences (India)

    adrenocortical (HPA) axis which regulates secretion of the stress responsive corticosteroids. The hippocampus is known to provide an inhibitory feedback to the HPA axis. Hippocampal damage then would result in disinhibition of the HPA axis ...

  3. Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Muzaffar, Suhail; Chattoo, Bharat B

    2017-03-01

    Anacardic acid is a medicinal phytochemical that inhibits proliferation of fungal as well as several types of cancer cells. It induces apoptotic cell death in various cell types, but very little is known about the mechanism involved in the process. Here, we used budding yeast Saccharomyces cerevisiae as a model to study the involvement of some key elements of apoptosis in the anacardic acid-induced cell death. Plasma membrane constriction, chromatin condensation, DNA degradation, and externalization of phosphatidylserine (PS) indicated that anacardic acid induces apoptotic cell death in S. cerevisiae. However, the exogenous addition of broad-spectrum caspase inhibitor Z-VAD-FMK or deletion of the yeast caspase Yca1 showed that the anacardic acid-induced cell death is caspase independent. Apoptosis-inducing factor (AIF1) deletion mutant was resistant to the anacardic acid-induced cell death, suggesting a key role of Aif1. Overexpression of Aif1 made cells highly susceptible to anacardic acid, further confirming that Aif1 mediates anacardic acid-induced apoptosis. Interestingly, instead of the increase in the intracellular reactive oxygen species (ROS) normally observed during apoptosis, anacardic acid caused a decrease in the intracellular ROS levels. Quantitative real-time PCR analysis showed downregulation of the BIR1 survivin mRNA expression during the anacardic acid-induced apoptosis.

  4. Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Fenger, Christina; Nielsen, Helle H

    2004-01-01

    degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly...... larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed...

  5. Acid-induced equilibrium folding intermediate of human platelet profilin.

    Science.gov (United States)

    McLachlan, Glendon D; Cahill, Sean M; Girvin, Mark E; Almo, Steven C

    2007-06-12

    The acid-induced unfolding of human platelet profilin (HPP) can be minimally modeled as a three-state process. Equilibrium unfolding studies have been performed on human platelet profilin1 (HPP) and monitored by far-UV circular dichroism, tryptophan fluorescence, ANS binding, and NMR spectroscopy. Far-UV CD measurements obtained by acid titration demonstrate that HPP unfolds via a three-state mechanism (N --> I --> U), with a highly populated intermediate between pH 4 and 5. Approximately 80% of native helical secondary structural content remains at pH 4, as indicated by monitoring the CD signal at 222 nm. The stability (DeltaGH2O) of the native conformation at pH 7.0 (obtained by monitoring the change in tryptophan signal as a function of urea concentration) is 5.56 +/- 0.51 kcal mol-1; however, the DeltaGH2O for the intermediate species at pH 4 is 2.01 +/- 0.47 kcal mol-1. The calculated m-values for the pH 7.0 and pH 4.0 species were 1.64 +/- 0.15 and 1.34 +/- 0.17 kcal mol-1 M-1, respectively, which is an indication that the native and intermediate species are similarly compact. Additionally, translational diffusion measurements obtained by NMR spectroscopy and ANS binding studies are consistent with a globular and compact conformation at both pH 7.0 and 4.0. The pKa values for the two histidine (His) residues located on helix 4 of HPP were determined to be 5.6 and 5.7 pH units. These pKa values coincide with the midpoint of the far-UV CD acid titration curve and suggest that the protonation of one or both His residues may play a role in the formation of the unfolding intermediate. Stable intermediate species populate the 2D 1H-15N HSQC NMR spectra between pH 4 and 5. A number of backbone and side-chain resonances show significant perturbations relative to the native spectrum; however, considerable nativelike tertiary contacts remain. Interestingly, the residues on HPP that are significantly altered at low pH coincide with segments of the G-actin binding

  6. [Lattice degeneration of the retina].

    Science.gov (United States)

    Boĭko, E V; Suetov, A A; Mal'tsev, D S

    2014-01-01

    Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

  7. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Nabi Shamsaei

    2015-01-01

    Full Text Available Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks. Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  8. Distribution of hippocampal mossy fibers in the rat. An experimental study with silver impregnation methods

    DEFF Research Database (Denmark)

    Blackstad, T W; Brink, K; Hem, J

    1970-01-01

    The paper deals with the distribution of the axons that arise in the fascia dentata and go to the hippocampus proper. lesions were placed in the fascia dentata and degenerating mossy fibers were mapped by silver impregnation, mostly according to the method of Fink and Heimer ('67). The fascia....... Mossy fibers do not enter the fimbria at any point. Degenerating fibers can be traced to the limit between regio superior (CA 1) and regio inferior. This dentato‐hippocampal connection displays a pattern of precise localization, each level of fascia dentata projecting onto a restricted level of regio...... inferior. The bands of degenerated mossy fibers produced by lesions in the fascia dentata were largely oriented in the transverse direction (slightly in a temporal direction) and were somewhat wider distally than at the origin from the hilus. Very narrow bands were seen in a few animals with particularly...

  9. Hippocampal polysynaptic computation.

    Science.gov (United States)

    Kimura, Rie; Kang, Siu; Takahashi, Naoya; Usami, Atsushi; Matsuki, Norio; Fukai, Tomoki; Ikegaya, Yuji

    2011-09-14

    Neural circuitry is a self-organizing arithmetic device that converts input to output and thereby remodels its computational algorithm to produce more desired output; however, experimental evidence regarding the mechanism by which information is modified and stored while propagating across polysynaptic networks is sparse. We used functional multineuron calcium imaging to monitor the spike outputs from thousands of CA1 neurons in response to the stimulation of two independent sites of the dentate gyrus in rat hippocampal networks ex vivo. Only pyramidal cells were analyzed based on post hoc immunostaining. Some CA1 pyramidal cells were observed to fire action potentials only when both sites were simultaneously stimulated (AND-like neurons), whereas other neurons fired in response to either site of stimulation but not to concurrent stimulation (XOR-like neurons). Both types of neurons were interlaced in the same network and altered their logical operation depending on the timing of paired stimulation. Repetitive paired stimulation for brief periods induced a persistent reorganization of AND and XOR operators, suggesting a flexibility in parallel distributed processing. We simulated these network functions in silico and found that synaptic modification of the CA3 recurrent excitation is pivotal to the shaping of logic plasticity. This work provides new insights into how microscopic synaptic properties are associated with the mesoscopic dynamics of complex microcircuits.

  10. Degenerate asymptotic perturbation theory

    International Nuclear Information System (INIS)

    Hunziker, W.; Pillet, C.A.

    1983-01-01

    Asymptotic Rayleigh-Schroedinger perturbation theory for discrete eigenvalues is developed systematically in the general degenerate case. For this purpose we study the spectral properties of mxm - matrix functions A(kappa) of a complex variable kappa which have an asymptotic expansion ΣAsub(k)kappasup(k) as kappa->0. We show that asymptotic expansions for groups of eigenvalues and for the corresponding spectral projections of A(kappa) can be obtained from the set [Asub(k)] by analytic perturbation theory. Special attention is given to the case where A(kappa) is Borel-summable in some sector originating from kappa=0 with opening angle >π. Here we prove that the asymptotic series describe individual eigenvalues and eigenprojections of A(kappa) which are shown to be holomorphic in S near kappa=0 and Borel summable if Asub(k)sup(*)=Asub(k) for all k. We then fit these results into the scheme of Rayleigh-Schroedinger perturbation theory and we give some examples of asymptotic estimates for Schroedinger operators. (orig.)

  11. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); H.H.H. Adams (Hieab); N. Jahanshad (Neda); G. Chauhan (Ganesh); J.L. Stein; E. Hofer (Edith); M.E. Rentería (Miguel); J.C. Bis (Joshua); A. Arias-Vásquez (Alejandro); Ikram, M.K. (M. Kamran); S. Desrivières (Sylvane); M.W. Vernooij (Meike); L. Abramovic (Lucija); S. Alhusaini (Saud); N. Amin (Najaf); M. Andersson (Micael); K. Arfanakis (Konstantinos); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); L. Athanasiu (Lavinia); T. Axelsson (Tomas); A.H. Beecham (Ashley); A. Beiser (Alexa); M. Bernard (Manon); S.H. Blanton (Susan H.); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.M. Brickman (Adam M.); Carmichael, O. (Owen); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); V. Chouraki (Vincent); G. Cuellar-Partida (Gabriel); F. Crivello (Fabrice); A. den Braber (Anouk); Doan, N.T. (Nhat Trung); S.M. Ehrlich (Stefan); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); R.F. Gottesman (Rebecca); O. Grimm (Oliver); M.D. Griswold (Michael); T. Guadalupe (Tulio); Gutman, B.A. (Boris A.); J. Hass (Johanna); U.K. Haukvik (Unn); D. Hoehn (David); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); Jørgensen, K.N. (Kjetil N.); N. Karbalai (Nazanin); D. Kasperaviciute (Dalia); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil); D.C. Liewald (David C.); L.M. Lopez (Lorna); M. Luciano (Michelle); C. MacAre (Christine); Marquand, A.F. (Andre F.); M. Matarin (Mar); R. Mather; M. Mattheisen (Manuel); McKay, D.R. (David R.); Milaneschi, Y. (Yuri); S. Muñoz Maniega (Susana); K. Nho (Kwangsik); A.C. Nugent (Allison); P. Nyquist (Paul); Loohuis, L.M.O. (Loes M. Olde); J. Oosterlaan (Jaap); M. Papmeyer (Martina); Pirpamer, L. (Lukas); B. Pütz (Benno); A. Ramasamy (Adaikalavan); Richards, J.S. (Jennifer S.); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); N. Rommelse (Nanda); S. Ropele (Stefan); E.J. Rose (Emma); N.A. Royle (Natalie); T. Rundek (Tatjana); P.G. Sämann (Philipp); Saremi, A. (Arvin); C.L. Satizabal (Claudia L.); L. Schmaal (Lianne); N.J. Schork (Nicholas); Shen, L. (Li); J. Shin (Jean); Shumskaya, E. (Elena); A.V. Smith (Albert Vernon); R. Sprooten (Roy); V.M. Strike (Vanessa); A. Teumer (Alexander); D. Tordesillas-Gutierrez (Diana); R. Toro (Roberto); D. Trabzuni (Danyah); S. Trompet (Stella); D. Vaidya (Dhananjay); J. van der Grond (Jeroen); S.J. van der Lee (Sven); Van Der Meer, D. (Dennis); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); T.G.M. van Erp (Theo G.); Van Rooij, D. (Daan); E. Walton (Esther); L.T. Westlye (Lars); C.D. Whelan (Christopher); B.G. Windham (B Gwen); A.M. Winkler (Anderson); K. Wittfeld (Katharina); G. Woldehawariat (Girma); A. Björnsson (Asgeir); Wolfers, T. (Thomas); L.R. Yanek (Lisa); Yang, J. (Jingyun); A.P. Zijdenbos; M.P. Zwiers (Marcel); I. Agartz (Ingrid); L. Almasy (Laura); D.J. Ames (David); Amouyel, P. (Philippe); O.A. Andreassen (Ole); S. Arepalli (Sampath); A.A. Assareh; S. Barral (Sandra); M.E. Bastin (Mark); Becker, D.M. (Diane M.); J.T. Becker (James); D.A. Bennett (David A.); J. Blangero (John); H. van Bokhoven (Hans); D.I. Boomsma (Dorret); H. Brodaty (Henry); R.M. Brouwer (Rachel); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan); K. Bulayeva (Kazima); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); D.M. Cannon (Dara); G. Cavalleri (Gianpiero); Cheng, C.-Y. (Ching-Yu); S. Cichon (Sven); M.R. Cookson (Mark); A. Corvin (Aiden); B. Crespo-Facorro (Benedicto); J.E. Curran (Joanne); M. Czisch (Michael); A.M. Dale (Anders); G.E. Davies (Gareth); A.J. de Craen (Anton); E.J.C. de Geus (Eco); P.L. de Jager (Philip); G.I. de Zubicaray (Greig); I.J. Deary (Ian J.); S. Debette (Stéphanie); C. DeCarli (Charles); N. Delanty; C. Depondt (Chantal); A.L. DeStefano (Anita); A. Dillman (Allissa); S. Djurovic (Srdjan); D.J. Donohoe (Dennis); D.A. Drevets (Douglas); Duggirala, R. (Ravi); M.D. Dyer (Matthew); C. Enzinger (Christian); S. Erk; T. Espeseth (Thomas); Fedko, I.O. (Iryna O.); Fernández, G. (Guillén); L. Ferrucci (Luigi); S.E. Fisher (Simon); D. Fleischman (Debra); I. Ford (Ian); M. Fornage (Myriam); T. Foroud (Tatiana); P.T. Fox (Peter); C. Francks (Clyde); Fukunaga, M. (Masaki); Gibbs, J.R. (J. Raphael); D.C. Glahn (David); R.L. Gollub (Randy); H.H.H. Göring (Harald H.); R.C. Green (Robert C.); O. Gruber (Oliver); V. Gudnason (Vilmundur); S. Guelfi (Sebastian); Håberg, A.K. (Asta K.); N.K. Hansell (Narelle); J. Hardy (John); C.A. Hartman (C.); Hashimoto, R. (Ryota); K. Hegenscheid (Katrin); J. Heinz (Judith); S. Le Hellard (Stephanie); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); Ho, B.-C. (Beng-Choon); P.J. Hoekstra (Pieter); W. Hoffmann (Wolfgang); A. Hofman (Albert); F. Holsboer (Florian); G. Homuth (Georg); N. Hosten (Norbert); J.J. Hottenga (Jouke Jan); M.J. Huentelman (Matthew); H.H. Pol; Ikeda, M. (Masashi); Jack, C.R. (Clifford R.); S. Jenkinson (Sarah); R. Johnson (Robert); Jönsson, E.G. (Erik G.); J.W. Jukema; R. Kahn (René); Kanai, R. (Ryota); I. Kloszewska (Iwona); Knopman, D.S. (David S.); P. Kochunov (Peter); Kwok, J.B. (John B.); S. Lawrie (Stephen); H. Lemaître (Herve); X. Liu (Xinmin); D.L. Longo (Dan L.); O.L. Lopez (Oscar L.); S. Lovestone (Simon); Martinez, O. (Oliver); J.-L. Martinot (Jean-Luc); V.S. Mattay (Venkata S.); McDonald, C. (Colm); A.M. McIntosh (Andrew); McMahon, F.J. (Francis J.); McMahon, K.L. (Katie L.); P. Mecocci (Patrizia); I. Melle (Ingrid); Meyer-Lindenberg, A. (Andreas); S. Mohnke (Sebastian); Montgomery, G.W. (Grant W.); D.W. Morris (Derek W); T.H. Mosley (Thomas H.); T.W. Mühleisen (Thomas); B. Müller-Myhsok (B.); M.A. Nalls (Michael); M. Nauck (Matthias); T.E. Nichols (Thomas); W.J. Niessen (Wiro); M.M. Nöthen (Markus); L. Nyberg (Lars); Ohi, K. (Kazutaka); R.L. Olvera (Rene); R.A. Ophoff (Roel); M. Pandolfo (Massimo); T. Paus (Tomas); Z. Pausova (Zdenka); B.W.J.H. Penninx (Brenda); Pike, G.B. (G. Bruce); S.G. Potkin (Steven); B.M. Psaty (Bruce); S. Reppermund; M. Rietschel (Marcella); J.L. Roffman (Joshua); N. Seiferth (Nina); J.I. Rotter (Jerome I.); M. Ryten (Mina); Sacco, R.L. (Ralph L.); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); R. Schmidt (Reinhold); Schmidt, H. (Helena); C.J. Schofield (Christopher); Sigursson, S. (Sigurdur); Simmons, A. (Andrew); A. Singleton (Andrew); S.M. Sisodiya (Sanjay); Smith, C. (Colin); J.W. Smoller; H. Soininen (H.); V.M. Steen (Vidar); D.J. Stott (David J.); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); M. Tsolaki (Magda); C. Tzourio (Christophe); A.G. Uitterlinden (André); Hernández, M.C.V. (Maria C. Valdés); M.P. van der Brug (Marcel); A. van der Lugt (Aad); N.J. van der Wee (Nic); N.E.M. van Haren (Neeltje E.); D. van 't Ent (Dennis); M.J.D. van Tol (Marie-José); B.N. Vardarajan (Badri); B. Vellas (Bruno); D.J. Veltman (Dick); H. Völzke (Henry); H.J. Walter (Henrik); J. Wardlaw (Joanna); A.M.J. Wassink (Annemarie); M.E. Weale (Michael); Weinberger, D.R. (Daniel R.); Weiner, M.W. (Michael W.); Wen, W. (Wei); E. Westman (Eric); T.J.H. White (Tonya); Wong, T.Y. (Tien Y.); Wright, C.B. (Clinton B.); R.H. Zielke (Ronald H.); A.B. Zonderman; N.G. Martin (Nicholas); C.M. van Duijn (Cornelia); M.J. Wright (Margaret); W.T. Longstreth Jr; G. Schumann (Gunter); H.J. Grabe (Hans Jörgen); B. Franke (Barbara); L.J. Launer (Lenore); S.E. Medland (Sarah Elizabeth); S. Seshadri (Sudha); P.M. Thompson (Paul); M.K. Ikram (Kamran)

    2017-01-01

    textabstractThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic

  12. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; van der Grond, Jeroen; van der Lee, Sven J.; van der Meer, Dennis; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; van Erp, Theo G. M.; van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; de Craen, Anton J. M.; de Geus, Eco J. C.; de Jager, Philip L.; de Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; Decarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; van Haren, Neeltje E. M.; van 't Ent, Dennis; van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

    2017-01-01

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of

  13. Novel genetic loci associated with hippocampal volume

    OpenAIRE

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

    2017-01-01

    International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

  14. Computed tomography of Wallerian degeneration

    International Nuclear Information System (INIS)

    Uchino, Akira; Maeda, Fumihiko

    1986-01-01

    CT findings of wallerian degeneration of the pyramidal tract at the midbrain (atrophy of cerebral peduncle following cerebrovascular accident) were studied in 34 patients (44 CT scans) with old cerebrovascular accidents. Severe atrophy of cerebral peduncle was noted when the ipsilateral motor cortex was involved. However, when the posterior limb of the internal capsule was involved, atrophy of the ipsilateral cerebral peduncle was mild. In this series, the shortest interval between cerebrovascular accident and wallerian degeneration was 8 month. (author)

  15. Hippocampal Sclerosis in Older Patients: Practical Examples and Guidance With a Focus on Cerebral Age-Related TDP-43 With Sclerosis.

    Science.gov (United States)

    Cykowski, Matthew D; Powell, Suzanne Z; Schulz, Paul E; Takei, Hidehiro; Rivera, Andreana L; Jackson, Robert E; Roman, Gustavo; Jicha, Gregory A; Nelson, Peter T

    2017-08-01

    - Autopsy studies of the older population (≥65 years of age), and particularly of the "oldest-old" (≥85 years of age), have identified a significant proportion (∼20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. - To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). - Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. - In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology.

  16. Ascorbic Acid Induces Necrosis in Human Laryngeal Squamous Cell Carcinoma via ROS, PKC, and Calcium Signaling.

    Science.gov (United States)

    Baek, Min-Woo; Cho, Heui-Seung; Kim, Sun-Hun; Kim, Won-Jae; Jung, Ji-Yeon

    2017-02-01

    Ascorbic acid induces apoptosis, autophagy, and necrotic cell death in cancer cells. We investigated the mechanisms by which ascorbic acid induces death in laryngeal squamous cell carcinoma Hep2 cells. Ascorbic acid markedly reduced cell viability and induced death without caspase activation and an increase in cytochrome c. Hep2 cells exposed to ascorbic acid exhibited membrane rupture and swelling, the morphological characteristics of necrotic cell death. The generation of reactive oxygen species (ROS) was increased in Hep2 cells treated with ascorbic acid, and pretreatment with N-acetylcysteine blocked ascorbic acid-induced cell death. Ascorbic acid also stimulated protein kinase C (PKC) signaling, especially PKC α/β activation, and subsequently increased cytosolic calcium levels. However, ascorbic acid-induced necrotic cell death was inhibited by Ro-31-8425 (PKC inhibitor) and BAPTA-AM (cytosolic calcium-selective chelator). ROS scavenger NAC inhibited PKC activation induced by ascorbic acid and Ro-31-8425 suppressed the level of cytosolic calcium increased by ascorbic acid, indicating that ROS is represented as an upstream signal of PKC pathway and PKC activation leads to the release of calcium into the cytosol, which ultimately regulates the induction of necrosis in ascorbic acid-treated Hep2 cells. These data demonstrate that ascorbic acid induces necrotic cell death through ROS generation, PKC activation, and cytosolic calcium signaling in Hep2 cells. J. Cell. Physiol. 232: 417-425, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Comparison of Hippocampal Volume in Dementia Subtypes

    International Nuclear Information System (INIS)

    Vijayakumar, Avinash; Vijayakumar, Abhishek

    2012-01-01

    Aims. To examine the relationship between different types of dementia and hippocampal volume. Methods. Hippocampal volume was measured using FL3D sequence magnetic resonance imaging in 26 Alzheimer's, vascular dementia, mixed dementia, and normal pressure hydrocephalus patients and 15 healthy controls and also hippocampal ratio, analyzed. Minimental scale was used to stratify patients on cognitive function impairments. Results. Hippocampal volume and ratio was reduced by 25% in Alzheimer's disease, 21% in mixed dementia, 11% in vascular dementia and 5% in normal pressure hydrocephalus in comparison to control. Also an asymmetrical decrease in volume of left hippocampus was noted. The severity of dementia increased in accordance to decreasing hippocampal volume. Conclusion. Measurement in hippocampal volume may facilitate in differentiating different types of dementia and in disease progression. There was a correlation between hippocampal volume and severity of cognitive impairment

  18. Valproic acid-induced pancreatitis in a 15-year-old boy with juvenile myoclonic epilepsy.

    Science.gov (United States)

    Veri, Kadi; Uibo, Oivi; Talvik, Inga; Talvik, Tiina

    2013-01-01

    Drug-induced acute pancreatitis is a rare condition in childhood, and information about the incidence of valproic acid-induced acute pancreatitis in the pediatric population is scarce. In this clinical case, we report a first documented pediatric case of valproic acid-induced pancreatitis in Estonia. A 15-year-old boy with juvenile myoclonic epilepsy developed acute pancreatitis after 2-month therapy with valproic acid. The symptoms of pancreatitis subsided within 1 week after the discontinuation of treatment with valproic acid. Acute pancreatitis should be suspected in any pediatric patient with gastrointestinal symptoms during valproate treatment.

  19. Sleep benefits subsequent hippocampal functioning

    NARCIS (Netherlands)

    van der Werf, Y.D.; Altena, E.; Schoonheim, M.M.; Sanz-Arigita, E.J.; Vis, J.C.; de Rijke, W.; van Someren, E.J.

    2009-01-01

    Sleep before learning benefits memory encoding through unknown mechanisms. We found that even a mild sleep disruption that suppressed slow-wave activity and induced shallow sleep, but did not reduce total sleep time, was sufficient to affect subsequent successful encoding-related hippocampal

  20. Hippocampal Sclerosis: Causes and Prevention.

    Science.gov (United States)

    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  2. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    Science.gov (United States)

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

  3. Bile Acid-induced Apoptosis in Hepatocytes Is Caspase-6-dependent

    NARCIS (Netherlands)

    Rust, Christian; Wild, Nadine; Bernt, Carina; Vennegeerts, Timo; Wimmer, Ralf; Beuers, Ulrich

    2009-01-01

    Apoptosis induced by hydrophobic bile acids is thought to contribute to liver injury during cholestasis. Caspase-6 is an executioner caspase that also appears to have regulatory functions in hematopoetic cell lines. We aimed to elucidate the role of caspase-6 in bile acid-induced apoptosis. The

  4. Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature

    Science.gov (United States)

    Ighodaro, Eseosa T.; Jicha, Gregory A.; Schmitt, Frederick A.; Neltner, Janna H.; Abner, Erin L.; Kryscio, Richard J.; Smith, Charles D.; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J.; Nelson, Peter T.

    2015-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with “hippocampal sclerosis” pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of “segmental” HS-Aging in which “sclerosis” in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of “hippocampal sclerosis” and TDP-43 pathologies in aged subjects. PMID:26083567

  5. Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature.

    Science.gov (United States)

    Ighodaro, Eseosa T; Jicha, Gregory A; Schmitt, Frederick A; Neltner, Janna H; Abner, Erin L; Kryscio, Richard J; Smith, Charles D; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J; Nelson, Peter T

    2015-07-01

    Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with "hippocampal sclerosis" pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of "segmental" HS-Aging in which "sclerosis" in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of "hippocampal sclerosis" and TDP-43 pathologies in aged subjects.

  6. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  7. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wanjiku Mathenge

    2014-12-01

    Full Text Available Age-related macular degeneration (AMD is a disease of the retina that usually develops in people aged 60 years and older. It affects about 8.7% of the world’s population and is the leading cause of blindness among people aged 50 and older in industrialised countries.

  8. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Degenerated differential pair with controllable transconductance

    NARCIS (Netherlands)

    Mensink, Clemens; Mensink, Clemens H.J.; Nauta, Bram

    1998-01-01

    A differential pair with input transistors and provided with a variable degeneration resistor. The degeneration resistor comprises a series arrangement of two branches of coupled resistors which are shunted in mutually corresponding points by respective control transistors whose gates are

  10. Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy and hippocampal sclerosis.

    Science.gov (United States)

    Schijns, Olaf; Karaca, Ümit; Andrade, Pablo; de Nijs, Laurence; Küsters, Benno; Peeters, Andrea; Dings, Jim; Pannek, Heinz; Ebner, Alois; Rijkers, Kim; Hoogland, Govert

    2015-10-01

    To determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. The hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (psclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls. Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (psclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosis patients remain to be studied. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat.

    Science.gov (United States)

    Jain, S; Shukla, S D; Sharma, K; Bhatnagar, M

    2001-09-01

    The neuroprotective effects of W. somnifera were studied on stressed adult female Swiss albino rats. Experimental rats were subjected to immobilization stress for 14 h and were treated with a root powder extract of W. somnifera available as Stresscom capsules (Dabur India Ltd). Control rats were maintained in completely, non stressed conditions. Thionin stained serial coronal sections (7 microm) of brain passing through the hippocampal region of stressed rats (E(1) group) demonstrated 85% degenerating cells (dark cells and pyknotic cells) in the CA(2) and CA(3) sub-areas. Treatment with W. somnifera root powder extract significantly reduced (80%) the number of degenerating cells in both the areas. The study thus demonstrates the antistress neuroprotective effects of W. somnifera. Copyright 2001 John Wiley & Sons, Ltd.

  12. Increased synthesis of heparin affin regulatory peptide in the perforant path lesioned mouse hippocampal formation

    DEFF Research Database (Denmark)

    Poulsen, F R; Lagord, C; Courty, J

    2000-01-01

    differentiation in vivo. Here we have investigated the expression of HARP mRNA and protein in the perforant path lesioned C57B1/6 mouse hippocampal formation from 1 to 35 days after surgery. This type of lesion induces a dense anterograde and terminal axonal degeneration, activation of glial cells, and reactive...... axonal sprouting within the perforant path zones of the fascia dentata and hippocampus as well as axotomy-induced retrograde neuronal degeneration in the entorhinal cortex. Analysis of sham- and unoperated control mice showed that HARP mRNA is expressed in neurons and white and gray matter glial cells...... as well as vascular and pial cells throughout the normal, adult brain. Lesioning induced high levels of HARP mRNA in astroglial-like cells in the denervated zones of fascia dentata and hippocampus as soon as day 2 postlesion. This expression reached maximum at day 4, and declined toward normal at day 7...

  13. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M M; Duncan, J L

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  14. Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease dementia.

    Science.gov (United States)

    Wang, Pei-Ning; Chou, Kun-Hsien; Chang, Ni-Jung; Lin, Ker-Neng; Chen, Wei-Ta; Lan, Gong-Yau; Lin, Ching-Po; Lirng, Jiing-Feng

    2014-04-01

    Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single-domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Copyright © 2013 Wiley Periodicals, Inc.

  15. Acetic acid induces a programmed cell death process in the food spoilage yeast Zygosaccharomyces bailii.

    Science.gov (United States)

    Ludovico, Paula; Sansonetty, Filipe; Silva, Manuel T; Côrte-Real, Manuela

    2003-03-01

    Here we show that 320-800 mM acetic acid induces in Zygosaccharomyces bailii a programmed cell death (PCD) process that is inhibited by cycloheximide, is accompanied by structural and biochemical alterations typical of apoptosis, and occurs in cells with preserved mitochondrial and plasma membrane integrity (as revealed by rhodamine 123 (Rh123) and propidium iodide (PI) staining, respectively). Mitochondrial ultrastructural changes, namely decrease of the cristae number, formation of myelinic bodies and swelling were also seen. Exposure to acetic acid above 800 mM resulted in killing by necrosis. The occurrence of an acetic acid-induced active cell death process in Z. bailii reinforces the concept of a physiological role of the PCD in the normal yeast life cycle.

  16. Caffeic Acid Induced Apoptosis in MG63 Osteosarcoma Cells Through Activation of Caspases

    Directory of Open Access Journals (Sweden)

    Ferry Sandra

    2017-03-01

    Full Text Available Background: Caffeic acid has been reported that when it is combined with all-trans retinoic acid, it can inhibit proliferation activity of SaOS-2 or OSA-01 cells. In addition, caffeic acid merely could reduce cell viability of SaOS-2 cells. However, there is not any study in caffeic acid's possible effect to induce apoptosis in osteosarcoma cell. Materials and Methods: MG-63 cells were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum. Cells were treated with various concentrations of caffeic acid. Apoptosis were analyzed with Sub-G1 assay and activation of caspase-8, -9, and -3 were analyzed with immunoblotting. Caffeic acid-induced percentage of apoptotic cells and cleaved-8, -9, -3 were then statistically analyzed. Results: Sub-G1 results showed that caffeic acid significantly induced apoptosis in MG-63 osteosarcoma cells in concentration dependent manner. Immunoblotting results showed that caffeic acid induced cleavage of caspase-8, -9 and -3. Cleaved-caspase-8 and -9 were increased at 1-hour treatment of caffeic acid, while cleaved-caspase 3 was increased markedly at 6-hours treatment of caffeic acid. Conclusions: Caffeic acid induces apoptosis significantly in concentration dependent manner through caspase-dependent intrinsic apoptotic pathway. Keywords: caffeic acid, osteosarcoma, MG-63, apoptosis, caspase

  17. Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

    Directory of Open Access Journals (Sweden)

    Daniele Bertoglio

    2017-11-01

    Full Text Available The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE. As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE. Wistar Han (Charles River, France and Sprague-Dawley (Harlan, The Netherlands rats were subjected to KASE using the Hellier kainic acid (KA and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG in a subgroup of animals, while animals were sacrificed 1 week (subacute phase and 12 weeks (chronic phase post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei, microglial activation (OX-42 and translocator protein, and neurodegeneration (Fluorojade C were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001 in SD/H (median 8.3 days animals compared to WH/CR (median 15.4 days. During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01. However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure

  18. Disc degeneration: current surgical options

    Directory of Open Access Journals (Sweden)

    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

  19. Lattice degeneration of the retina.

    Science.gov (United States)

    Byer, N E

    1979-01-01

    Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

  20. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  1. Novel genetic loci associated with hippocampal volume.

    Science.gov (United States)

    Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

    2017-01-18

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

  2. CDK5 knockdown prevents hippocampal degeneration and cognitive dysfunction produced by cerebral ischemia

    OpenAIRE

    Gutiérrez-Vargas, Johana A; Múnera, Alejandro; Cardona-Gómez, Gloria P

    2015-01-01

    Acute ischemic stroke is a cerebrovascular accident and it is the most common cause of physical disabilities around the globe. Patients may present with repeated ictuses, experiencing mental consequences, such as depression and cognitive disorders. Cyclin-dependent kinase 5 (CDK5) is a kinase that is involved in neurotransmission and plasticity, but its dysregulation contributes to cognitive disorders and dementia. Gene therapy targeting CDK5 was administered to the right hippocampus of ische...

  3. CDK5 knockdown prevents hippocampal degeneration and cognitive dysfunction produced by cerebral ischemia.

    Science.gov (United States)

    Gutiérrez-Vargas, Johana A; Múnera, Alejandro; Cardona-Gómez, Gloria P

    2015-12-01

    Acute ischemic stroke is a cerebrovascular accident and it is the most common cause of physical disabilities around the globe. Patients may present with repeated ictuses, experiencing mental consequences, such as depression and cognitive disorders. Cyclin-dependent kinase 5 (CDK5) is a kinase that is involved in neurotransmission and plasticity, but its dysregulation contributes to cognitive disorders and dementia. Gene therapy targeting CDK5 was administered to the right hippocampus of ischemic rats during transient cerebral middle artery occlusion. Physiologic parameters (blood pressure, pH, pO2, and pCO2) were measured. The CDK5 downregulation resulted in neurologic and motor improvement during the first week after ischemia. Cyclin-dependent kinase 5 RNA interference (RNAi) prevented dysfunctions in learning, memory, and reversal learning at 1 month after ischemia. These observations were supported by the prevention of neuronal loss, the reduction of microtubule-associated protein 2 (MAP2) immunoreactivity, and a decrease in astroglial and microglia hyperreactivities and tauopathy. Additionally, CDK5 silencing led to an increase in the expression of brain-derived neurotrophic factor (BDNF), its Tropomyosin Receptor kinase B (TRKB) receptor, and activation of cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinase (ERK), which are important targets in neuronal plasticity. Together, our findings suggest that gene therapy based on CDK5 silencing prevents cerebral ischemia-induced neurodegeneration and motor and cognitive deficits.

  4. PHOTODYNAMIC THERAPY OF MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    Davorin Sevšek

    2004-05-01

    Full Text Available Background. University Eye Clinic in Ljubljana began to perform a photodynamic therapy (PDT in July 2002. Up to September 2003 there were 51 PDT interventions on 36 eyes. Almost half of the eyes had one or more reinterventions. PDT was used on 29 eyes with age related macular degeneration (AMD. Just before the treatment all of them had visual acuity (VA 6/60 or better and there were predominantly classical or classical choroidal neovascular (CNV membranes. Most VA did not changed significantly in follow-up visits but diameter of CNV membranes was obviously reduced. In macular degeneration due to pathologic myopia (MMD, photodynamic therapy was performed on 7 eyes with mainly occult CNV and VA was 12/60 or better. VA was mostly better in follow-up visits than before treatment with PDT.Conclusions. There were no serious complications during and after PDT interventions. Two patients had back pain during the infusion of Verteporfin but there was no need to stop the intervention.

  5. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Querques G

    2011-05-01

    Full Text Available Giuseppe Querques¹, Fernando Onofrio Avellis1,2, Lea Querques1,3, Francesco Bandello³, Eric H Souied¹ ¹Service d'Ophtalmologie, Centre Hospitalier Intercommunal Créteil, Université Paris-Est Créteil, Créteil, France; ²Parma Eye Clinic University Hospital, Università degli Studi di Parma, Parma, Italy; ³Department of Ophthalmology, Università Vita-Salute San Raffaele Milano, Milano, Italy Date of preparation: March 3, 2011 Conflict of interest: None declaredClinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD?Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches.Implementation: strategy of administration, safety of intravitreal injectionKeywords: age-related macular degeneration, antivascular endothelial growth factor, choroidal neovascularization, drusen, geographic atrophy

  6. Imaging of corticobasal degeneration syndrome

    International Nuclear Information System (INIS)

    Koyama, Masamichi; Yagishita, Akira; Nakata, Yasuhiro; Hayashi, Masaharu; Bandoh, Mitsuaki; Mizutani, Toshio

    2007-01-01

    Diagnosing corticobasal degeneration is often difficult on the basis of clinical symptoms and radiological images. We aimed to clarify the imaging findings of corticobasal degeneration syndrome (CBDS). Included in the study were 16 patients (8 men, 8 women, 46-75 years old) with clinically diagnosed CBDS. We evaluated the patients' symptoms and signs, and MR and single-photon emission CT (SPECT) imaging findings. All the patients had cerebral atrophy. Asymmetric cerebral atrophy was observed in 13 patients (81%) predominantly contralateral to the side clinically more affected. Atrophy in the cerebral peduncle was observed in seven patients. FLAIR images showed hyperintensity in the subcortical white matter in the frontoparietal lobes in the clinically more affected side in 14 patients, and in the rolandic region in 13 patients. Asymmetric hypoperfusion in the frontoparietal lobes on SPECT images was observed in all of the patients, and in the basal ganglia in 11 patients. CBDS might be unique in showing hyperintensity in the subcortical white matter in the rolandic region on FLAIR images with asymmetric atrophy predominantly contralateral to the side clinically more severely affected. Asymmetric atrophy in the cerebral peduncle without signal abnormalities was also characteristic of CBDS. Atrophy in the midbrain tegmentum was also seen in patients with CBDS. (orig.)

  7. Visual performance of pigeons following hippocampal lesions.

    Science.gov (United States)

    Bingman, V P; Hodos, W

    1992-11-15

    The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

  8. APP/Go protein Gβγ-complex signaling mediates Aβ degeneration and cognitive impairment in Alzheimer's disease models.

    Science.gov (United States)

    Bignante, Elena Anahi; Ponce, Nicolás Eric; Heredia, Florencia; Musso, Juliana; Krawczyk, María C; Millán, Julieta; Pigino, Gustavo F; Inestrosa, Nibaldo C; Boccia, Mariano M; Lorenzo, Alfredo

    2018-04-01

    Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation. Gallein, a selective pharmacological inhibitor of Gβγ complex, inhibited Aβ-induced dendritic and axonal dystrophy, abnormal tau phosphorylation, synaptic loss, and neuronal cell death in hippocampal neurons expressing endogenous protein levels. In the 3xTg-AD mice, intrahippocampal application of gallein reversed memory impairment associated with early Aβ pathology. Our data provide further evidence for the involvement of APP/Go protein in Aβ-induced degeneration and reveal that Gβγ complex is a signaling target potentially relevant for developing therapies for halting Aβ degeneration in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  10. Global hypoxia induced impairment in learning and spatial memory is associated with precocious hippocampal aging.

    Science.gov (United States)

    Biswal, Suryanarayan; Sharma, Deepti; Kumar, Kushal; Nag, Tapas Chandra; Barhwal, Kalpana; Hota, Sunil Kumar; Kumar, Bhuvnesh

    2016-09-01

    Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory. Copyright © 2016. Published by Elsevier Inc.

  11. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  12. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  13. Inflammatory profiles in canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Tellegen, Anna R; Bergknut, Niklas; Creemers, Laura B; Wolfswinkel, Jeannette; Freudigmann, Christian; Benz, Karin; Grinwis, Guy C M; Tryfonidou, Marianna A; Meij, Björn P

    2016-01-01

    BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene

  14. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  15. Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-Mei; Zheng, Yuan-Lin; Hu, Bin; Cheng, Wei; Zhang, Zi-Feng

    2012-02-01

    Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  16. Hippocampal synaptic plasticity, spatial memory and anxiety

    OpenAIRE

    Bannerman, David M.; Sprengel, Rolf; Sanderson, David J.; McHugh, Stephen B.; Rawlins, J. Nicholas P.; Monyer, Hannah; Seeburg, Peter H.

    2014-01-01

    Recent studies using transgenic mice lacking NMDA receptors in the hippocampus challenge the long-standing hypothesis that hippocampal long-term potentiation-like mechanisms underlie the encoding and storage of associative long-term spatial memories. However, it may not be the synaptic plasticity-dependent memory hypothesis that is wrong; instead, it may be the role of the hippocampus that needs to be re-examined. We present an account of hippocampal function that explains its role in both me...

  17. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    International Nuclear Information System (INIS)

    Okujava, M.; Ebner, A.; Schmitt, J.; Woermann, F.G.

    2002-01-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  18. Hippocampal correlates of aversive mibdrain stimulation.

    Science.gov (United States)

    Routtenberg, A; Kramis, R C

    1968-06-21

    Hippocampal synchronization during aversive dorsal midbrain stimulation was observed in rats both in a conditioning procedure and under d-tubo-curarine paralysis. The results restrict the generality of previous reports which correlated hippocampal synchronization and desynchronization with approach and withdrawal behavior, respectively. Relative to the condition of free movement, curarization reduced the frequency of both "spontaneous" and dorsal midbrain-evoked synchronization, thus suggesting possible direct and indirect effects of d-tubocurarine on subcortical structures.

  19. Naturalness of nearly degenerate neutrinos

    CERN Document Server

    Casas, J A; Ibarra, Alejandro; Navarro, I

    1999-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate. We study whether radiative corrections can or cannot be responsible for the small mass splittings, in agreement with all the available experimental data. We perform an exhaustive exploration of the bimaximal mixing scenario, finding that (i) the vacuum oscillations solution to the solar neutrino problem is always excluded; (ii) if the mass matrix is produced by a see-saw mechanism, there are large regions of the parameter space consistent with the large angle MSW solution, providing a natural origin for the Delta m^2_{sol} << Delta m^2_{atm} hierarchy; (iii) the bimaximal structure becomes then stable under radiative corrections. We also provide analytical expressions for the mass splittings and mixing angles and present a particularly simple see-saw ansatz consistent with all the observations.

  20. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  1. Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

    Science.gov (United States)

    Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

    2012-01-01

    Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

  2. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis. © The Author(s) 2015.

  3. Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

    Science.gov (United States)

    Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

    2015-02-01

    Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Science.gov (United States)

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-05

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Protective Effects of Nigella Sativaon Acetylsalicylic Acid-Induced Nephrotoxicity in Albino Rats.

    Science.gov (United States)

    Asif, Sania; Malik, Lubna

    2017-09-01

    To see the effects of Nigella sativaon acetylsalicylic acid-induced nephrotoxicity in albino rats. An experimental study. The Anatomy Department of University of Health Sciences, Lahore, from January 2014 to December 2015. Thirty-two female albino rats were divided into four groups. Group A(control) was given single dose of 10 mg/100 gm body weight of 1% methylcellulose, orally. Group B and C were treated with oral 1000 mg/kg acetylsalicylic acid as a single dose. Group D was given 250 mg/kg ethanolic extract of Nigella sativa(NSE) by oral gavage followed by single dose of 1000 mg/kg acetylsalicylic acid on 1st day of experiment; after that only NSE was continued till 7 days. Animals of groups A, C and D were sacrificed on day 8 and that of group B on day 2 of experiment. Cardiac puncture was performed to draw blood from each animal for renal function tests. Animals were evaluated for gross (Paired kidney weight, body weight, relative tissue body weight index) as well as for biochemical (Serum urea and creatinine) parameters. Gross as well as biochemical parameters were markedly impaired in group B, but statistically significant improvement was noticed in Nigella sativatreated group. There was no self recovery in group C. Ethanolic extract of Nigella sativahas a protective role against acetylsalicylic acid-induced nephrotoxicity in albino rats.

  6. Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease.

    Science.gov (United States)

    Nelson, Peter T; Smith, Charles D; Abner, Erin L; Wilfred, Bernard J; Wang, Wang-Xia; Neltner, Janna H; Baker, Michael; Fardo, David W; Kryscio, Richard J; Scheff, Stephen W; Jicha, Gregory A; Jellinger, Kurt A; Van Eldik, Linda J; Schmitt, Frederick A

    2013-08-01

    Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.

  7. Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

    Science.gov (United States)

    Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

    2013-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

  8. Hippocampal EEG and behaviour in dog. II. Hippocampal EEG correlates with elementary motor acts

    NARCIS (Netherlands)

    Arnolds, D.E.A.T.; Lopes da Silva, F.H.; Aitink, J.W.; Kamp, A.

    A positive correlation has been shown between the speed of forced stepping on a conveyor belt and the amplitude and frequency of the concomitant hippocampal EEG. Significant modulation in the spectral properties of the dog's hippocampal EEG has been found in relation to 3 elementary motor acts:

  9. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.

    Science.gov (United States)

    Quiroz, Yakeel T; Budson, Andrew E; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E

    2010-12-01

    The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Twenty carriers of the Alzheimer's-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.

  10. Characterizing degenerate Sturm-Liouville problems

    Directory of Open Access Journals (Sweden)

    Angelo B. Mingarelli

    2004-11-01

    Full Text Available Consider the Dirichlet eigenvalue problem associated with the real two-term weighted Sturm-Liouville equation $$-(p(xy'' = lambda r(xy$$ on the finite interval [a,b]. This eigenvalue problem will be called degenerate provided its spectrum fills the whole complex plane. Generally, in degenerate cases the coefficients $p(x, r(x$ must each be sign indefinite on [a,b]. Indeed, except in some special cases, the quadratic forms induced by them on appropriate spaces must also be indefinite. In this note we present a necessary and sufficient condition for this boundary problem to be degenerate. Some extensions are noted.

  11. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  12. Mouse models for cone degeneration.

    Science.gov (United States)

    Samardzija, Marijana; Grimm, Christian

    2014-01-01

    Loss of cone vision has devastating effects on everyday life. Even though much effort has been made to understand cone physiology and pathophysiology, no successful therapies are available for patients suffering from cone disorders. As complex retinal interactions cannot be studied in vitro, utilization of different animal models is inevitable. Due to recent advances in transgenesis, mice became the most popular animal model to study human diseases, also in ophthalmology. While there are similarities in retinal anatomy and pathophysiology between mice and humans, there are also differences, most importantly the lack of a cone-rich macula in mice. Instead, cones in mice are rare and distributed over the whole retina, which makes the analysis of cone pathophysiology very difficult in these animals. This hindrance is one of the reasons why our understanding of rod pathophysiological processes is much more advanced. Recently, however, the sparseness of cones was overcome by the generation of the Nrl (- / -) mouse that expresses only cone photoreceptors in the retina. This paper will give a brief overview of some of the known mouse models to study cone degeneration and discuss the current knowledge gained from the analysis of these models.

  13. Degeneration of biogenic superparamagnetic magnetite.

    Science.gov (United States)

    Li, Y-L; Pfiffner, S M; Dyar, M D; Vali, H; Konhauser, K; Cole, D R; Rondinone, A J; Phelps, T J

    2009-01-01

    Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 h incubation and 5-year anaerobic storage were investigated with transmission electron microscopy, Mössbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 h and 5-year crystals are 8.4164A and 8.3774A, respectively. The Mössbauer spectra indicated that the 265 h magnetite had excess Fe(II) in its crystal-chemistry (Fe(3+) (1.990)Fe(2+) (1.015)O(4)) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe(3+) (2.388)Fe(2+) (0.419)O(4)). Such crystal-chemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases (fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the anaerobic oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

  14. Degeneration of Biogenic Superparamagnetic Magnetite

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dr. Yi-Liang [University of Tennessee, Knoxville (UTK); Pfiffner, Susan M. [University of Tennessee, Knoxville (UTK); Dyar, Dr. M Darby [Mount Holyoke College; Vali, Dr. Hojatolah [McGill University, Montreal, Quebec; Konhauser, Dr, Kurt [University of Alberta; Cole, David R [ORNL; Rondinone, Adam Justin [ORNL; Phelps, Tommy Joe [ORNL

    2009-01-01

    ABSTRACT. Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 hours incubation and 5-year storage were investigated with transmission electron microscopy, M ssbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 hour and 5-year crystals are 8.4164 and 8.3774 , respectively. The M ssbauer spectra indicated that the 265 hour magnetite had excess Fe(II) in its crystal-chemistry (Fe3+1.9901Fe2+ 1.0149O4) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe3+2.3875Fe2+0.4188O4). Such crystal-hemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases(fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

  15. Very Degenerate Higgsino Dark Matter

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Eung Jin [Korea Institute for Advanced Study,Seoul 130-722 (Korea, Republic of); Jung, Sunghoon [SLAC National Accelerator Laboratory,Menlo Park, CA 94025 (United States); Kavli Institute for Theoretical Physics,Santa Barbara, CA 93106 (United States); Park, Jong-Chul [Department of Physics, Chungnam National University,Daejeon 34134 (Korea, Republic of)

    2017-01-03

    We present a study of the Very Degenerate Higgsino Dark Matter (DM), whose mass splitting between the lightest neutral and charged components is O(1) MeV, much smaller than radiative splitting of 355 MeV. The scenario is realized in the minimal supersymmetric standard model by small gaugino mixings. In contrast to the pure Higgsino DM with the radiative splitting only, various observable signatures with distinct features are induced. First of all, the very small mass splitting makes (a) sizable Sommerfeld enhancement and Ramsauer-Townsend (RT) suppression relevant to ∼1 TeV Higgsino DM, and (b) Sommerfeld-Ramsauer-Townsend effect saturate at lower velocities v/c≲10{sup −3}. As a result, annihilation signals can be large enough to be observed from the galactic center and/or dwarf galaxies, while the relative signal sizes can vary depending on the locations of Sommerfeld peaks and RT dips. In addition, at collider experiments, stable chargino signatures can be searched for to probe the model in the future. DM direct detection signals, however, depend on the Wino mass; even no detectable signals can be induced if the Wino is heavier than about 10 TeV.

  16. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had......% (psample the second peak was not identified. Conclusion: Protective effects of experimentally developed salivary pellicles can be related to their protein composition, although, not all proteins could be identified in this study......., and one Chinese. After collection, saliva was dialysed and lyophilised and re-dissolved at 0.5% in Type I water. Next, four polished bovine enamel specimens were immersed into each sample under gentle and constant shaking for 12 hours. Last, specimens were exposed to an erosive challenge of pH 2.3 for 4...

  17. Raw data of the effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity

    Directory of Open Access Journals (Sweden)

    Alarcón-Herrera Norberto

    2017-10-01

    Full Text Available The raw data showed in this article comes from the published research article entitled “Protective effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity” Food Chem Toxicol. 2017 May 3. pii: S0278-6915(1730226-0. DOI:10.1016/j.fct.2017.04.048. [1]. Data illustrates antitoxic and antigenotoxic effects of Chlorogenic acid (CGA on toxicity and genotoxicity produced by the in vivo treatment with mitochondria toxin 3-Nitropropionic acid (3-NP in mice. Toxicity and genotoxicity was evaluated in erythrocytes of peripheral blood through the micronuclei assay. Data was share at the Elsevier repository under the reference number FCT9033.

  18. Unsaturated fatty acids protect trophoblast cells from saturated fatty acid-induced autophagy defects.

    Science.gov (United States)

    Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki

    2018-02-01

    Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Acid-Induced Rearrangement of Epoxygermacranolides: Synthesis of Furanoheliangolides and Cadinanes from Nobilin

    Directory of Open Access Journals (Sweden)

    Maria De Mieri

    2017-12-01

    Full Text Available The acid-induced rearrangement of three epoxyderivatives of nobilin 1, the most abundant sesquiterpene lactone in Anthemis nobilis flowers, was investigated. From the 1,10-epoxyderivative 2, furanoheliangolide 5 was obtained, while the 4,5-epoxy group of 3 did not react. Conversely, when the 3-hydroxy function of nobilin was acetylated (12, the 4,5-epoxy derivative did cyclize into cadinanes (15 and 16 under Lewis acid catalysis. The reactivity of the 4,5- and 1,10-epoxy derivatives of nobilin (2 and 3 was compared with that of parthenolide, and rationalized on the basis of quantum chemical calculations. All isolated reaction products were fully characterized by spectroscopic and computational methods, and their in vitro anti-protozoal activity was evaluated. The paper could provide new insights into the biosynthesis of this class of natural products.

  20. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    Science.gov (United States)

    Rego, António; Duarte, Ana M.; Azevedo, Flávio; Sousa, Maria J.; Côrte-Real, Manuela; Chaves, Susana R.

    2014-01-01

    Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria. PMID:28357256

  1. Determination of the pK for the acid-induced denaturation of ferrocytochrome c.

    Science.gov (United States)

    Varhac, Rastislav; Antalík, Marián

    2004-03-30

    Optical absorption spectroscopy was used to characterize the acid-induced conformational transition of horse heart ferrocytochrome c in the presence of urea. By using linear extrapolation to zero denaturant concentration, an apparent pK value for denaturation was found to be 0.86 +/- 0.07 at 25 degrees C. Visible absorption spectra in the presence of high urea concentration indicate that the dominant population is a high-spin, five-coordinate form under acidic conditions. Ferricytochrome c, used as a model reference system, shows a linear dependence of pK values versus urea concentration in the range from 0 to 4.1 M. Our data also indicate that even at a pH below 2 the iron-sulfur bond in ferrocytochrome c is present.

  2. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

    Science.gov (United States)

    Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

    2014-01-01

    Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

  3. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

  4. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  5. Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation.

    Science.gov (United States)

    Lee, Jae Kyoo; Nam, Hong Gil; Zare, Richard N

    2017-01-01

    Kinetics of acid-induced chlorophyll demetallation was recorded in microdroplets by fusing a stream of microdroplets containing 40 µM chlorophyll a or b dissolved in methanol with a stream of aqueous microdroplets containing 35 mM hydrochloric acid (pH = 1·46). The kinetics of the demetallation of chlorophyll in the fused microdroplets (14 ± 6 µm diameter; 84 ± 18 m s-1 velocity) was recorded by controlling the traveling distance of the fused microdroplets between the fusion region and the inlet of a mass spectrometer. The rate of acid-induced chlorophyll demetallation was about 960 ± 120 times faster in the charged microdroplets compared with that reported in bulk solution. If no voltage was applied to the sprayed microdroplets, then the acceleration factor was about 580 ± 90, suggesting that the applied voltage is not a major factor determining the acceleration. Chlorophyll a was more rapidly demetallated than chlorophyll b by a factor of ~26 in bulk solution and ~5 in charged microdroplets. The demetallation kinetics was second order in the H+ concentration, but the acceleration factor of microdroplets compared with bulk solution appeared to be unchanged in going from pH = 1·3 to 7·0. The water:methanol ratio of the fused microdroplets was varied from 7:3 to 3:7 causing an increase in the reaction rate of chlorophyll a demetallation by 20%. This observation demonstrates that the solvent composition, which has different evaporation rates, does not significantly affect the acceleration. We believe that a major portion of the acceleration can be attributed to confinement effects involving surface reactions rather than either to evaporation of solvents or to the introduction of charges to the microdroplets.

  6. Evidence connecting old, new and neglected glucose-lowering drugs to bile acid-induced GLP-1 secretion

    DEFF Research Database (Denmark)

    Kårhus, Martin L; Brønden, Andreas; Sonne, David P

    2017-01-01

    Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have...... current evidence connecting established glucose-lowering drugs to bile acid-induced GLP-1 secretion and discusses whether bile acid-induced GLP-1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium-dependent bile acids transporter, and bile acid...... sequestrants - old, new and neglected glucose-lowering drugs - improve glucose metabolism....

  7. Magnetic resonance imaging of intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Maeda, Hiroshi; Noguchi, Masao; Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi.

    1993-01-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.)

  8. Magnetic resonance imaging of intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

    1993-02-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

  9. The nature of apraxia in corticobasal degeneration.

    OpenAIRE

    Leiguarda, R; Lees, A J; Merello, M; Starkstein, S; Marsden, C D

    1994-01-01

    Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia...

  10. Myxomatous degeneration of the lumbar intervertebral disc.

    Science.gov (United States)

    Beatty, R A

    1985-08-01

    Sixteen patients were operated on for lumbar pain and pain radiating into the sciatic nerve distribution. In all 16, when the anulus fibrosus was incised, soft, gray disc material extruded under pressure like toothpaste being squeezed from a tube. This syndrome of myxomatous degeneration is a distinct entity, different from classical fibrotic disc degeneration or herniated nucleus pulposus. Surgical removal associated with partial facetectomy produced excellent results. The concept of incompetence of the anulus fibrosis is discussed.

  11. Hamiltonization of theories with degenerate coordinates

    International Nuclear Information System (INIS)

    Gitman, D.M.; Tyutin, I.V.

    2002-01-01

    We consider a class of Lagrangian theories where part of the coordinates does not have any time derivatives in the Lagrange function (we call such coordinates degenerate). We advocate that it is reasonable to reconsider the conventional definition of singularity based on the usual Hessian and, moreover, to simplify the conventional hamiltonization procedure. In particular, in such a procedure, it is not necessary to complete the degenerate coordinates with the corresponding conjugate momenta

  12. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  13. Adult hippocampal neurogenesis and cognitive aging

    Directory of Open Access Journals (Sweden)

    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  14. 3T MRI quantification of hippocampal volume and signal in mesial temporal lobe epilepsy improves detection of hippocampal sclerosis.

    Science.gov (United States)

    Coan, A C; Kubota, B; Bergo, F P G; Campos, B M; Cendes, F

    2014-01-01

    In mesial temporal lobe epilepsy, MR imaging quantification of hippocampal volume and T2 signal can improve the sensitivity for detecting hippocampal sclerosis. However, the current contributions of these analyses for the diagnosis of hippocampal sclerosis in 3T MRI are not clear. Our aim was to compare visual analysis, volumetry, and signal quantification of the hippocampus for detecting hippocampal sclerosis in 3T MRI. Two hundred three patients with mesial temporal lobe epilepsy defined by clinical and electroencephalogram criteria had 3T MRI visually analyzed by imaging epilepsy experts. As a second step, we performed automatic quantification of hippocampal volumes with FreeSurfer and T2 relaxometry with an in-house software. MRI of 79 healthy controls was used for comparison. Visual analysis classified 125 patients (62%) as having signs of hippocampal sclerosis and 78 (38%) as having normal MRI findings. Automatic volumetry detected atrophy in 119 (95%) patients with visually detected hippocampal sclerosis and in 10 (13%) with visually normal MR imaging findings. Relaxometry analysis detected hyperintense T2 signal in 103 (82%) patients with visually detected hippocampal sclerosis and in 15 (19%) with visually normal MR imaging findings. Considered together, volumetry plus relaxometry detected signs of hippocampal sclerosis in all except 1 (99%) patient with visually detected hippocampal sclerosis and in 22 (28%) with visually normal MR imaging findings. In 3T MRI visually inspected by experts, quantification of hippocampal volume and signal can increase the detection of hippocampal sclerosis in 28% of patients with mesial temporal lobe epilepsy.

  15. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

    2001-01-01

    ) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed...... by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

  16. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Thiébaud, P

    2001-01-01

    In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn......) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized......-methyl-D-aspartate (NMDA) and the neurotoxin trimethyltin (TMT), as demonstrated by the cellular uptake of propidium iodide (PI), which was used as a reproducible and quantifiable marker for neuronal degeneration. We conclude that organotypic brain slice cultures can grow on silicon-based three-dimensional microelectrode...

  17. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  18. NEURONAL DEGENERATION, SYNAPTIC DEFECTS, AND BEHAVIORAL ABNORMALITIES IN TAU45-230 TRANSGENIC MICE

    Science.gov (United States)

    Lang, Ashlee E.; Methner, D. Nicole Riherd; Ferreira, Adriana

    2014-01-01

    The complement of mechanisms underlying tau pathology in neurodegenerative disorders has yet to be elucidated. Among these mechanisms, abnormal tau phosphorylation has received the most attention because neurofibrillary tangles present in Alzheimer’s disease (AD) and related disorders known as tauopathies are composed of hyperphosphorylated forms of this microtubule-associated protein. More recently, we showed that calpain-mediated cleavage leading to the generation of the 17 kDa tau45-230 fragment is a conserved mechanism in these diseases. To obtain insights into the role of this fragment in neurodegeneration, we generated transgenic mice that express tau45-230 and characterized their phenotype. Our results showed a significant increase in cell death in the hippocampal pyramidal cell layer of transgenic tau45-230 mice when compared to wild type controls. In addition, significant synapse loss was detected as early as six months after birth in transgenic hippocampal neurons. These synaptic changes were accompanied by alterations in the expression of the N-methyl-D-aspartate glutamate (NMDA) receptor subunits. Furthermore, functional abnormalities were detected in the transgenic mice using Morris Water Maze and fear conditioning tests. These results suggest that the accumulation of tau45-230 is responsible, at least in part, for neuronal degeneration and some behavioral changes in AD and other tauopathies. Collectively, these data provide the first direct evidence of the toxic effects of a tau fragment biologically produced in the context of these diseases in vertebrate neurons that develop in situ. PMID:24952329

  19. Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells

    Directory of Open Access Journals (Sweden)

    Seon Min Woo

    2018-04-01

    Full Text Available Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor, necroptosis inhibitor (necrostatin-1, or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO. Furthermore, corosolic acid significantly induces reactive oxygen species (ROS levels, but antioxidants (N-acetyl-l-cysteine (NAC and trolox do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498, breast cancer (MDA-MB231, and hepatocellular carcinoma (SK-Hep1 and Huh7 cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.

  20. Hippocampal insulin resistance and cognitive dysfunction

    NARCIS (Netherlands)

    Biessels, Geert Jan; Reagan, Lawrence P.

    2015-01-01

    Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as

  1. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  2. Glucocorticoid receptor knockdown and adult hippocampal neurogenesis

    NARCIS (Netherlands)

    Hooijdonk, Leonarda Wilhelmina Antonia van

    2010-01-01

    The research in this thesis is aimed at the elucidation of the role of the glucocorticoid receptor (GR) in hippocampal neuroplasticity and functioning. To achieve this, we have developed a novel method to specifically knockdown GR in a discrete cell population of the mouse brain. In this thesis I

  3. Resveratrol: A Potential Hippocampal Plasticity Enhancer.

    Science.gov (United States)

    Dias, Gisele Pereira; Cocks, Graham; do Nascimento Bevilaqua, Mário Cesar; Nardi, Antonio Egidio; Thuret, Sandrine

    2016-01-01

    The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN), can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by "nutraceutical" agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions.

  4. Hippocampal theta frequency shifts and operant behaviour

    NARCIS (Netherlands)

    Lopes da Silva, F.H.; Kamp, A.

    1. 1. A shift of hippocampal dominant theta frequency to 6 c/sec has been demonstrated in the post-reward period in two dogs, which occurs consistently related in time to a well defined behavioural pattern in the course of an operant conditioning paradigm. 2. 2. The frequency shift was detected and

  5. Stimulus Configuration, Classical Conditioning, and Hippocampal Function.

    Science.gov (United States)

    Schmajuk, Nestor A.; DiCarlo, James J.

    1991-01-01

    The participation of the hippocampus in classical conditioning is described in terms of a multilayer network portraying stimulus configuration. A model of hippocampal function is presented, and computer simulations are used to study neural activity in the various brain areas mapped according to the model. (SLD)

  6. Amnesia due to bilateral hippocampal glioblastoma

    International Nuclear Information System (INIS)

    Shimauchi, M.; Wakisaka, S.; Kinoshita, K.

    1989-01-01

    The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a 'butterfly' lesion, it is unusual for it to invade the limbic system selectively to this extent. (orig.)

  7. Nocturnal mnemonics: sleep and hippocampal memory processing.

    Science.gov (United States)

    Saletin, Jared M; Walker, Matthew P

    2012-01-01

    As critical as waking brain function is to learning and memory, an established literature now describes an equally important yet complementary role for sleep in information processing. This overview examines the specific contribution of sleep to human hippocampal memory processing; both the detriments caused by a lack of sleep, and conversely, the proactive benefits that develop following the presence of sleep. First, a role for sleep before learning is discussed, preparing the hippocampus for initial memory encoding. Second, a role for sleep after learning is considered, modulating the post-encoding consolidation of hippocampal-dependent memory. Third, a model is outlined in which these encoding and consolidation operations are symbiotically accomplished, associated with specific NREM sleep physiological oscillations. As a result, the optimal network outcome is achieved: increasing hippocampal independence and hence overnight consolidation, while restoring next-day sparse hippocampal encoding capacity for renewed learning ability upon awakening. Finally, emerging evidence is considered suggesting that, unlike previous conceptions, sleep does not universally consolidate all information. Instead, and based on explicit as well as saliency cues during initial encoding, sleep executes the discriminatory offline consolidation only of select information. Consequently, sleep promotes the targeted strengthening of some memories while actively forgetting others; a proposal with significant theoretical and clinical ramifications.

  8. Nocturnal Mnemonics: Sleep and Hippocampal Memory Processing

    Directory of Open Access Journals (Sweden)

    Jared M. Saletin

    2012-05-01

    Full Text Available As critical as waking brain function is to learning and memory, an established literature now describes an equally important yet complementary role for sleep in information processing. This overview examines the specific contribution of sleep to human hippocampal memory processing; both the detriments caused by a lack of sleep, and conversely, the proactive benefits that develop following the presence of sleep. First, a role for sleep before learning is discussed, preparing the hippocampus for initial memory encoding. Second, a role for sleep after learning is considered, modulating the post-encoding consolidation of hippocampal-dependent memory. Third, a model is outlined in which these encoding and consolidation operations are symbiotically accomplished, associated with specific NREM sleep physiological oscillations. As a result, the optimal network outcome is achieved, increasing hippocampal independence and hence overnight consolidation, while restoring next-day sparse hippocampal encoding capacity for renewed learning ability upon awakening. Finally, emerging evidence is considered suggesting that, unlike previous conceptions, sleep does not universally consolidate all information equally. Instead, and based on explicit as well as motivational cues during initial encoding, sleep executes the discriminatory offline consolidation only of select information. Consequently, sleep promotes the targeted strengthening of some memories while actively forgetting others; a proposal with significant theoretical and clinical ramifications.

  9. Klotho regulates CA1 hippocampal synaptic plasticity.

    Science.gov (United States)

    Li, Qin; Vo, Hai T; Wang, Jing; Fox-Quick, Stephanie; Dobrunz, Lynn E; King, Gwendalyn D

    2017-04-07

    Global klotho overexpression extends lifespan while global klotho-deficiency shortens it. As well, klotho protein manipulations inversely regulate cognitive function. Mice without klotho develop rapid onset cognitive impairment before they are 2months old. Meanwhile, adult mice overexpressing klotho show enhanced cognitive function, particularly in hippocampal-dependent tasks. The cognitive enhancing effects of klotho extend to humans with a klotho polymorphism that increases circulating klotho and executive function. To affect cognitive function, klotho could act in or on the synapse to modulate synaptic transmission or plasticity. However, it is not yet known if klotho is located at synapses, and little is known about its effects on synaptic function. To test this, we fractionated hippocampi and detected klotho expression in both pre and post-synaptic compartments. We find that loss of klotho enhances both pre and post-synaptic measures of CA1 hippocampal synaptic plasticity at 5weeks of age. However, a rapid loss of synaptic enhancement occurs such that by 7weeks, when mice are cognitively impaired, there is no difference from wild-type controls. Klotho overexpressing mice show no early life effects on synaptic plasticity, but decreased CA1 hippocampal long-term potentiation was measured at 6months of age. Together these data suggest that klotho affects cognition, at least in part, by regulating hippocampal synaptic plasticity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. The neuronal ceroid lipofuscinosis Cln8 gene expression is developmentally regulated in mouse brain and up-regulated in the hippocampal kindling model of epilepsy

    Directory of Open Access Journals (Sweden)

    Kuronen Mervi

    2005-04-01

    Full Text Available Abstract Background The neuronal ceroid lipofuscinoses (NCLs are a group of inherited neurodegenerative disorders characterized by accumulation of autofluorescent material in many tissues, especially in neurons. Mutations in the CLN8 gene, encoding an endoplasmic reticulum (ER transmembrane protein of unknown function, underlie NCL phenotypes in humans and mice. The human phenotype is characterized by epilepsy, progressive psychomotor deterioration and visual loss, while motor neuron degeneration (mnd mice with a Cln8 mutation show progressive motor neuron dysfunction and retinal degeneration. Results We investigated spatial and temporal expression of Cln8 messenger ribonucleic acid (mRNA using in situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR and northern blotting. Cln8 is ubiquitously expressed at low levels in embryonic and adult tissues. In prenatal embryos Cln8 is most prominently expressed in the developing gastrointestinal tract, dorsal root ganglia (DRG and brain. In postnatal brain the highest expression is in the cortex and hippocampus. Expression of Cln8 mRNA in the central nervous system (CNS was also analyzed in the hippocampal electrical kindling model of epilepsy, in which Cln8 expression was rapidly up-regulated in hippocampal pyramidal and granular neurons. Conclusion Expression of Cln8 in the developing and mature brain suggests roles for Cln8 in maturation, differentiation and supporting the survival of different neuronal populations. The relevance of Cln8 up-regulation in hippocampal neurons of kindled mice should be further explored.

  11. Antinociceptive Effect of Ondansetron in Albino Mice Using Acetic Acid Induced Writhing Model

    Directory of Open Access Journals (Sweden)

    Abhay Purohit

    2016-10-01

    Full Text Available Background: Pain is an unpleasant sensory and emotional experience. Pain is a protective mechanism. Pain occurs whenever any tissues are being damaged, and it causes the individual to react and to remove the pain stimulus. Aim and Objectives: To evaluate the antinociceptive effect of ondansetron in comparison with the standard diclofenac. Material and Methods: The antinociceptive effect was tested by using the acetic acid induced writhing model in Swiss Albino mice. Animals were divided into 4 groups of 6 animals each. Animals were received distilled water (control, diclofenac (standard, ondansetron 0.5mg/kg (test I and ondansetron 1mg/kg (test II. After 30 minutes of drug administration, 0.1 ml of 1% acetic acid was injected. Mice were placed individually into glass beakers and five minutes were allowed to elapse. They were then observed for a period of ten minutes and the numbers of writhes were recorded in each animal. The results were expressed as mean ± SEM. One way ANOVA with post-test was used for statistical calculation. Results: The numbers of writhes were 1.33±0.494 for diclofenac; 6.33±1.872 and 9.33±1.706 for ondansetron 0.5 and 1mg/kg respectively. Conclusion: Ondansetron demonstrated statistical significant antinociceptive activity at both doses (0.5mg/kg and 1mg/kg and statistically similar effect as diclofenac

  12. Acid-induced autophagy protects human lung cancer cells from apoptosis by activating ER stress.

    Science.gov (United States)

    Xie, Wen-Yue; Zhou, Xiang-Dong; Li, Qi; Chen, Ling-Xiu; Ran, Dan-Hua

    2015-12-10

    An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly. In mouse tumors, the expression of cleaved caspase3 and p62 was enhanced by oral treatment with sodium bicarbonate, which can raise the intratumoral pH. Furthermore, the protein levels of ER stress markers, including p-PERK, p-eIF2α, CHOP, XBP-1s and GRP78, were also increased in response to acidic pH. The antioxidant NAC, which reduces ROS accumulation, alleviated acid-mediated ER stress and autophagy, and knocking down GRP78 reduced autophagy activation under acidic conditions, which suggests that autophagy was induced by acidic pH through ER stress. Taken together, these results indicate that the acidic microenvironment in non-small cell lung cancer cells promotes autophagy by increasing ROS-ER stress, which serves as a survival adaption in this setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Effect of galactose on acid induced molten globule state of Soybean Agglutinin: Biophysical approach

    Science.gov (United States)

    Alam, Parvez; Naseem, Farha; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2015-11-01

    In the present study the formation of molten globule-like unfolding intermediate Soybean Agglutinin (SBA) in acidic pH range has been established with the help of acrylamide quenching, intrinsic fluorescence, ANS fluorescence measurement, far UV CD and dynamic light scattering measurement. A marked increase in ANS fluorescence was observed at pH 2.2. Ksv of acrylamide quenching was found to be higher at pH 2.2 than that of native SBA at pH 7. Far UV CD spectra of pH induced state suggest that SBA shows significant retention of secondary structure closure to native. Hydrodynamic radius of SBA at pH 2.2 was found be more as compared to native state and also in other pH induced states. Further we checked the effect of galactose on the molten globule state of SBA. This study suggests that SBA exist as molten globule at pH 2.2 and this study will help in acid induced molten globule state of other proteins.

  14. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

    Directory of Open Access Journals (Sweden)

    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  15. Hexanoic acid-induced resistance against Botrytis cinerea in tomato plants.

    Science.gov (United States)

    Vicedo, Begonya; Flors, Víctor; de la O Leyva, María; Finiti, Ivan; Kravchuk, Zhana; Real, María Dolores; García-Agustín, Pilar; González-Bosch, Carmen

    2009-11-01

    We have demonstrated that root treatment with hexanoic acid protects tomato plants against Botrytis cinerea. Hexanoic acid-induced resistance (Hx-IR) was blocked in the jasmonic acid (JA)-insensitive mutant jai1 (a coi1 homolog) and in the abscisic acid (ABA)-deficient mutant flacca (flc). Upon infection, the LoxD gene as well as the oxylipin 12-oxo-phytodienoic acid and the bioactive molecule JA-Ile were clearly induced in treated plants. However, the basal ABA levels were not altered. Hexanoic acid primed callose deposition against B. cinerea in a cultivar-dependent manner. Treated plants from Ailsa Craig, Moneymaker, and Rheinlands Ruhm showed increased callose deposition but not from Castlemart. Hexanoic acid did not prime callose accumulation in flc plants upon B. cinerea infection; therefore, ABA could act as a positive regulator of Hx-IR by enhancing callose deposition. Furthermore, although hexanoic acid protected the JA-deficient mutant defensless1 (def1), the priming for callose was higher than in the wild type. This suggests a link between JA and callose deposition in tomato. Hence, the obtained results support the idea that callose, oxylipins, and the JA-signaling pathway are involved in Hx-IR against B. cinerea. Moreover our data support the relevance of JA-signaling for basal defense against this necrotroph in tomato. Hexanoic acid also protected against Pseudomonas syringae, indicating a broad-spectrum effect for this new inducer.

  16. PDIA3 Knockdown Exacerbates Free Fatty Acid-Induced Hepatocyte Steatosis and Apoptosis.

    Directory of Open Access Journals (Sweden)

    Xue-qun Zhang

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has emerged as one of the most common chronic liver disease over the past decades. Endoplasmic reticulum stress (ERS plays a pivotal role during the development of NAFLD. This study aims to analyze the potential role of protein disulfide isomerase A3 precursor (PDIA3, one of the ER chaperones, in free fatty acid-induced cell model of NAFLD. Human liver L02 cell line was treated with sodium palmitate for 24 hours, which developed severe intracellular lipid accumulation. The increased protein level of PDIA3 was detected via immunoblotting analysis in the fat loaded cell models of NAFLD. siRNA-mediated knockdown of PDIA3 in L02 cells not only increased the cellular lipid accumulation, but also exacerbated hepatocytes apoptosis induced by sodium palmitate. Further investigation revealed that knockdown of PDIA3 up-regulated protein expression of fatty acid synthase (FAS, a key enzyme involved in fatty acid synthesis. PDIA3 knockdown also up-regulated key molecules of ERS pathway, including glucose-regulated protein 78 (GRP78, phospho-PKR-like ER kinase (p-PERK, and C/EBP homologous protein (CHOP. Our results suggested that ER chaperone PDIA3 plays a pivotal role in FFA-induced hepatocyte steatosis and apoptosis.

  17. Fusobacterium nucleatum activates the immune response through retinoic acid-inducible gene I.

    Science.gov (United States)

    Lee, P; Tan, K S

    2014-02-01

    Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor involved in the sensing of RNA viruses and the initiation of antiviral responses. Fusobacterium nucleatum, a Gram-negative anaerobic bacterium associated with periodontal disease, is capable of invading cells. We hypothesized that F. nucleatum's ability to invade cells allows the microorganism to activate the immune response through RIG-I. Bacterial invasion was found to be necessary for F. nucleatum-induced nuclear factor kappa B (NF-κB) activation. Following invasion of the human periodontal ligament fibroblast (PDLF), F. nucleatum was located in the cytosol. F. nucleatum infection led to an 80-fold increase in RIG-I expression. Silencing RIG-I in PDLF by siRNA led to a significant decrease of NF-κB activation and expression of proinflammatory genes. Additionally, F. nucleatum was able to secrete nucleic acids, and introduction of F. nucleatum RNA into PDLF led to a RIG-I-dependent activation of NF-κB. Our findings showed RIG-I to be involved in the recognition of F. nucleatum. The function of RIG-I is likely to be broad and not limited to sensing of viruses only. Hence, this receptor may play an important role in detecting invasive forms of oral pathogens and contribute to inflammation in periodontal tissues.

  18. Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Takashi Yasukawa

    2012-11-01

    Full Text Available Elongin A increases the rate of RNA polymerase II (pol II transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A−/− embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A−/− embryonic stem cells (ESCs show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A−/− ESCs.

  19. Hippocampal phospho-tau/MAPT neuropathology in the fornix in Alzheimer disease: an immunohistochemical autopsy study.

    Science.gov (United States)

    Plowey, Edward D; Ziskin, Jennifer L

    2016-10-28

    Whereas early Alzheimer disease (AD) neuropathology and mild cognitive impairment are relatively common in aging, accurate prediction of patients that will progress to dementia requires new biomarkers. Recently, substantial work has focused on phospho-tau/MAPT (p-MAPT) neuropathology since its regional propagation correlates with the degree of cognitive impairment in AD. Recent diffusion tensor imaging studies in AD suggest that increased diffusion in the fornix secondary to p-MAPT-related axonal injury could serve as a predictive biomarker of the risk of disease progression. However, our knowledge of p-MAPT neuropathology in the fornix is limited. To address this gap in knowledge, we examined p-MAPT neuropathology in the fornix and basal forebrain nuclei via AT8 immunohistochemistry in 39 brain autopsies spanning the spectrum of AD neuropathologic changes. We found that the fornix and its precommissural efferent target nuclei (septum and nucleus accumbens) demonstrated neuronal and thread-like p-MAPT neuropathology only in National Institute on Aging/Alzheimer Association (NIA/AA) stages B2 and B3 of neurofibrillary degeneration, consistent with involvement after (and propagation from) the hippocampal formation. Interestingly, although tau astrogliopathy was frequently observed in the mammillary bodies in stage B2, neuronal tauopathy was not observed in the postcommissural targets (mammillary bodies and anterior thalamic nucleus) until stage B3. Tauopathy in the nucleus basalis of Meynert was strongly correlated with p-MAPT-positive axons in the fornix, suggesting that projections to the hippocampus also likely contribute to fornix tauopathy. Our cross-sectional autopsy findings indicate that the fornix is involved by p-MAPT neuropathology secondary to hippocampal involvement by AD neuropathology. Furthermore, our findings are compatible with the goal of in vivo detection of p-MAPT-related axonal pathology in the fornix in AD as a possible biomarker of p

  20. [Peripheral retinal degenerations--treatment recommendations].

    Science.gov (United States)

    Joussen, A M; Kirchhof, B

    2004-10-01

    This report reviews the clinical appearance of degenerative diseases of the peripheral retina in relationship to the risk of developing a rhegmatogenous retinal detachment. We present recommendations for preventive treatment in eyes at increased risk of developing retinal detachment. Retinal degenerations are common lesions involving the peripheral retina but most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and very rarely zonular traction tufts can result in rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic treatment; however, adequate studies have not been performed to date. Most of the peripheral retinal degenerations may not require treatment except in rare, high-risk situations. According to current knowledge there is no higher incidence of secondary pucker or other side effects after laser coagulation. Therefore, generous laser indication is recommended if risk factors apply.

  1. Families and degenerations of conformal field theories

    Energy Technology Data Exchange (ETDEWEB)

    Roggenkamp, D.

    2004-09-01

    In this work, moduli spaces of conformal field theories are investigated. In the first part, moduli spaces corresponding to current-current deformation of conformal field theories are constructed explicitly. For WZW models, they are described in detail, and sigma model realizations of the deformed WZW models are presented. The second part is devoted to the study of boundaries of moduli spaces of conformal field theories. For this purpose a notion of convergence of families of conformal field theories is introduced, which admits certain degenerated conformal field theories to occur as limits. To such a degeneration of conformal field theories, a degeneration of metric spaces together with additional geometric structures can be associated, which give rise to a geometric interpretation. Boundaries of moduli spaces of toroidal conformal field theories, orbifolds thereof and WZW models are analyzed. Furthermore, also the limit of the discrete family of Virasoro minimal models is investigated. (orig.)

  2. Intramuscular degeneration process in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Hasegawa, Takeshi; Matsumra, Kiichiro; Hashimoto, Takahiro; Ikehira, Hiroo; Fukuda, Hiroshi; Tateno, Yukio.

    1992-01-01

    Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T 1 -weighted longitudinal images (TR=215∼505 ms, TE=19∼20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author)

  3. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve disorders or injury. Following loss of axonal continuity, the isolated nerve stump distal to the lesion undergoes Wallerian degeneration in several phases. In the initial 'latent' phase...... at ankle distal to axotomy were monitored by 'threshold-tracking'. The plantar compound muscle action potentials (CMAPs) were recorded under anesthesia in three animal models: 8-week-old wild-type mice, 8-week-old slow Wallerian degeneration mutant mice and 3-year-old cats. We found that the progressive...... decrease in CMAP following crush injury was associated with slowing of conduction and marked abnormalities in excitability: increased peak threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus, enhanced superexcitability during the recovery cycle and increased rheobase...

  4. Phase space methods for degenerate quantum gases

    CERN Document Server

    Dalton, Bryan J; Barnett, Stephen M

    2015-01-01

    Recent experimental progress has enabled cold atomic gases to be studied at nano-kelvin temperatures, creating new states of matter where quantum degeneracy occurs - Bose-Einstein condensates and degenerate Fermi gases. Such quantum states are of macroscopic dimensions. This book presents the phase space theory approach for treating the physics of degenerate quantum gases, an approach already widely used in quantum optics. However, degenerate quantum gases involve massive bosonic and fermionic atoms, not massless photons. The book begins with a review of Fock states for systems of identical atoms, where large numbers of atoms occupy the various single particle states or modes. First, separate modes are considered, and here the quantum density operator is represented by a phase space distribution function of phase space variables which replace mode annihilation, creation operators, the dynamical equation for the density operator determines a Fokker-Planck equation for the distribution function, and measurable...

  5. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  6. Late complications following cryotherapy of lattice degeneration.

    Science.gov (United States)

    Benson, W E; Morse, P H; Nantawan, P

    1977-10-01

    We observed 341 patients who had received cryotherapy for lattice degeneration in order to identify possible late complications. Sequelae such as retinal tears posterior to an operculum or flap tears within treated areas showed that treatment did not necessarily prevent subsequent vitreous traction. Moreover, the newly created flap tears may extend beyond the treated area and can cause retinal detachment. Even scleral buckling did not necesserily prevent further traction. Therefore, we concluded that when cryotherapy is used to treat lattice degeneration, an adequate margin of surrounding retina should be treated and the treatment should extend to the ora serrata.

  7. Genetics of lattice degeneration of the retina.

    Science.gov (United States)

    Murakami, F; Ohba, N

    1982-01-01

    First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

  8. CT of sarcomatous degeneration in neurofibromatosis

    International Nuclear Information System (INIS)

    Coleman, B.G.; Arger, P.H.; Dalinka, M.K.; Obringer, A.C.; Raney, B.R.; Meadows, A.T.

    1983-01-01

    Neurofibromatosis is a relatively common disorder that often involves many organ systems. One of the least understood aspects of this malady is a well documented potential for sarcomatous degeneration of neurofibromas. The inability to identify patients at risk and the lack of noninvasive screening methods for symptomatic patients often leads to late diagnosis. In six of seven subsequently proven neurofibrosarcomas, CT demonstrated low-density areas that histopathologically appeared to be due to necrosis, hemorrhage, and/or cystic degeneration. The density differences within these sarcomas were enhanced by the intravenous adminstration of iodinated contrast agents

  9. Human sweet taste receptor mediates acid-induced sweetness of miraculin.

    Science.gov (United States)

    Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

    2011-10-04

    Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity.

  10. Praeruptorin D and E attenuate lipopolysaccharide/hydrochloric acid induced acute lung injury in mice.

    Science.gov (United States)

    Yu, Peng-Jiu; Li, Jing-Rong; Zhu, Zheng-Guang; Kong, Huan-Yu; Jin, Hong; Zhang, Jun-Yan; Tian, Yuan-Xin; Li, Zhong-Huang; Wu, Xiao-Yun; Zhang, Jia-Jie; Wu, Shu-Guang

    2013-06-15

    Acute lung injury is a life-threatening syndrome characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality rate worldwide. The dry root of Peucedanum praeruptorum Dunn has been long used to treat respiratory diseases in China. In the present study, Praeruptorin A, C, D and E (PA, PC, PD and PE), four pyranocoumarins extracted from this herb, have been investigated for the pharmacological effects in experimental lung injury mouse models. In lipopolysaccharide (LPS) challenged mice, PA and PC did not show protective effect against lung injury at the dose of 80 mg/kg. However, PD and PE significantly inhibited the infiltration of activated polymorphonuclear leukocytes (PMNs) and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid at the same dose. There was no statistically significant difference between PD and PE group. Further study demonstrated that PD and PE suppressed protein extravasations in bronchoalveolar lavage fluid, attenuated myeloperoxidase (MPO) activity and the pathological changes in the lung. Both PD and PE suppressed LPS induced Nuclear Factor-kappa B (NF-κB) pathway activation in the lung by decreasing the cytoplasmic loss of Inhibitor κB-α (IκB-α) protein and inhibiting the translocation of p65 from cytoplasm to nucleus. We also extended our study to acid-induced acute lung injury and found that these two compounds protected mice from hydrochloric acid (HCl)-induced lung injury by inhibiting PMNs influx, IL-6 release and protein exudation. Taken together, these results suggested that PD and PE might be useful in the therapy of lung injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  12. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  13. Effect of bevacizumab on acetic acid-induced ulcerative colitis in rats.

    Science.gov (United States)

    Ozsoy, Zeki; Ozsoy, Seyma; Gevrek, Fikret; Demir, Emre; Benli, Ismail; Daldal, Emin; Yenidogan, Erdinc

    2017-08-01

    The aim of this study was to examine the effect of intraperitoneally administered bevacizumab on colitis induced by acetic acid. An experimental model of acetic acid-induced colitis was introduced in rats. After the induction of colitis, bevacizumab was administered intraperitoneally at two different daily doses of low (2.5 mg/kg) or high (5 mg/kg) concentration. Control groups were included for colitis and bevacizumab. After 7 d, the rats were sacrificed, and colonic tissues were harvested for macroscopic and microscopic examination of colonic damage. Tumor necrosis factor alpha, interleukin 1 beta (IL-1β), IL-6, myeloperoxidase, malondialdehyde, glutathione, and superoxidismutase values were measured biochemically. There was no statistically significant macroscopic improvement in damage to the colon tissues (P > 0.05). The severity of inflammation was significantly reduced (0.98 ± 0.22) in the low-dose bevacizumab-treated rat group compared with the control group (P bevacizumab-treated rat group was not statistically significant (1.40 ± 0.33). In addition, although there was no significant change in the myeloperoxidase levels biochemically, IL-6 and malondialdehyde levels decreased in the low-dose treatment group (P = 0.014, P = 0.002, respectively). A significant decrease was found at both treatment doses in IL-1β (P bevacizumab were observed to have a protective effect in an experimental colitis model, and the dosage of 2.5 mg/kg bevacizumab was found to have a more prominent effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Cape Gooseberry [Physalis peruviana L.] Calyces Ameliorate TNBS Acid-induced Colitis in Rats.

    Science.gov (United States)

    Castro, Jenny; Ocampo, Yanet; Franco, Luis

    2015-11-01

    Physalis peruviana [cape gooseberry] is highly appreciated for its commercial value. The Colombian ecotype is in great demand in the international market, particularly for the unique morphological characteristics of the calyx, which has extended use as a traditional herbal remedy in Colombia because of its anti-inflammatory properties. In this work, the anti-inflammatory activity of the total ethereal extract of Physalis peruviana calyces was evaluated in preventive and therapeutic protocols in a TNBS acid-induced colitis rat model. Colitis was induced by intrarectal administration of TNBS. An evaluation of macroscopic and histopathological parameters in colonic tissue was performed, along with the determination of myeloperoxidase enzyme activity, cytokine levels and gene expression. Additionally, effects on nitric oxide release by lipopolysaccharide [LPS]-stimulated RAW264.7 macrophages and the scavenging activity of DPPH and ABTS free radicals were determined. The treatment with the Physalis peruviana extract produced a significant improvement in the colonic tissue at both macroscopic and histological levels. IL-1β and TNF-α production was reduced by the extract in both experimental approaches. The groups treated with Physalis peruviana showed a tendency to MUC2 up-regulation and down-regulation of COX-2, iNOS, NLRP3, IL-1β, IL-6 and IL-10 expression. Nitric oxide release in RAW264.7 macrophages was significantly inhibited. The Physalis peruviana extract showed intestinal anti-inflammatory activity in the TNBS-induced colitis model, placing this species' calyx, a natural derivative, as a promising source of metabolites that could be used in treatment for inflammatory bowel disease. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Nephroprotective effect of Corn Silk extract on oxalic acid-induced nephrocalcinosis in rabbit model

    Directory of Open Access Journals (Sweden)

    Faruk Hassan Al-Jawad

    2012-04-01

    Full Text Available ABSTRACT Background : Nephrocalcinosis is a state of deposition of calcium phosphate or oxalate in the renal parenchyma. It may occur in patients with renal tubular acidosis, vitamin D intoxication, and hyperparathyroidism. Corn silk was used in traditional Chinese medicine to relieve renal pains. Aim: To evaluate the effect of Corn silk aqueous extract in reducing calcium deposits from renal parenchyma in oxalic acid-induced nephrocalcinosis model. Materials and methods: Fourteen healthy rabbits were allocated to two groups. Two hours before induction of nephrocalcinosis, one group received water and the other received aqueous extract of corn silk and continued feeding for ten days. Blood samples were collected for biochemical analysis before induction and in the fifth and tenth post-induction day. Urine samples were taken to estimate urinary ca+2 levels and crystals. The histopathological examination was carried to check for crystal deposits in renal tissues. Results: Corn silk aqueous extract produced a significant reduction of blood urea nitrogen(5.2+/-0.08 vs 7.3+/-0.2 mmol/l, serum creatinine (85.9+/-0.2 vs 97.3+/-0.5 mmol/l and serum Na+ levels (137+/-0.2 vs 142.16+/-0.7 mmol/l with non-significant reduction in serum K+ (4.0+/-0.02 vs 4.2+/-0.05. There is a significant reduction in calcium deposition in renal parenchyma in comparison to the control group after ten days of treatment. Conclusion: Corn silk had a significant diuretic effect that accelerates the excretion of urinary calcium. [J Intercult Ethnopharmacol 2012; 1(2.000: 75-78

  16. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.

    Science.gov (United States)

    Beilke, Lisa D; Aleksunes, Lauren M; Olson, Erik R; Besselsen, David G; Klaassen, Curtis D; Dvorak, Katerina; Cherrington, Nathan J

    2009-07-10

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR(+/+) (WT) and CAR(-/-) (CAR-null) mice were pre-treated with compounds known to activate CAR prior to induction of intrahepatic cholestasis using the secondary bile acid lithocholic acid (LCA). Pre-treatment with the CAR activators phenobarbital (PB) and TCPOBOP (TC), as well as the non-CAR activator pregnenolone 16alpha-carbontrile (PCN), protected against LCA-induced liver injury in WT mice, whereas liver injury was more extensive without CAR (CAR-null). Unexpectedly, expression of anti-apoptotic Mcl-1 and Bcl-x(L) was not increased in hepatoprotected mice. Compared to unprotected groups, apoptosis was decreased in hepatoprotected mice as evidenced by the absence of cleaved caspase 3 (cCasp3). In contrast to the cytoplasmic localization in the injured livers (LCA and oltipraz), Mcl-1 protein was localized in the nucleus of hepatoprotected livers to potentially promote cell survival. This study demonstrates that although apoptosis is reduced in hepatoprotected mice pre-treated with CAR and non-CAR activators; hepatoprotection is not directly a result of CAR-induced Mcl-1 expression.

  17. Human sweet taste receptor mediates acid-induced sweetness of miraculin

    Science.gov (United States)

    Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

    2011-01-01

    Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity. PMID:21949380

  18. Nonthermal leptogenesis with almost degenerate superheavy neutrinos

    NARCIS (Netherlands)

    Allahverdi, Rouzbeh; Mazumdar, Anupam

    We present a model with minimal assumptions for nonthermal leptogenesis with almost degenerate superheavy right-handed neutrinos in a supersymmetric setup. In this scenario the gauge singlet inflaton is directly coupled to the right-handed (s)neutrinos with a mass heavier than the inflaton mass.

  19. Degenerate parabolic stochastic partial differential equations

    Czech Academy of Sciences Publication Activity Database

    Hofmanová, Martina

    2013-01-01

    Roč. 123, č. 12 (2013), s. 4294-4336 ISSN 0304-4149 R&D Projects: GA ČR GAP201/10/0752 Institutional support: RVO:67985556 Keywords : kinetic solutions * degenerate stochastic parabolic equations Subject RIV: BA - General Mathematics Impact factor: 1.046, year: 2013 http://library.utia.cas.cz/separaty/2013/SI/hofmanova-0397241.pdf

  20. MR findings of degenerating parenchymal neurocysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yul; Chung, Eun A; Yang, Ik; Park, Hae Jung; Chung, Soo Young [Hallym Univ. Kangnam Sungshim Hospital, Seoul (Korea, Republic of)

    1996-06-01

    To evaluate MR imaging findings of degenerating parenchymal neurocysticercosis and to determine the characteristics which distinguish it from other brain diseases. MR imagings of 19 patients (56 lesions) of degenerating parenchymal neurocysticercosis were retrospectively evaluated, focusing on the size and location of lesions signal intensity patterns of cyst fluid and wall, the extent of the surrounding edema and features of contrast enhancement. Degenerating parenchymal neurocysticercosis was located in gray or subcortical while matter in 89.3% of 56 lesions (50/56) ; most of these (98.2%) were smaller than 2 cm in diameter. Cyst fluid signal was hyperintense relative to CSF on T1 and proton density weighted images (92.9%). A hypointense signal rim of the cyst wall was noted in the lesions on proton density (92.9%) and T2 weighted (98.2%) images, Surrounding edema was mostly mild. Peripheral rim enhancement was noted in all lesions, and this was frequently irregular and lobulated (67.9%) with a focal defect in the enhancing rim(41.1%). Findings which could be helpful in distinguishing degenerating parencymal neurocysticercosis from other brain diseases are as follows : small, superficial lesions ; hyperintense signal of the cyst fluid on T1 and proton density weighted images ; hypointense signal of the cyst wall on proton density and T2 weighted images ; relatively mild extent of surrounding edema, and peripheral rim enhancement which is frequently irregular and lobulated with a focal defect in the enhancing rim.

  1. Geometry of non-degenerate Susskind fermions

    International Nuclear Information System (INIS)

    Mitra, P.

    1983-01-01

    The Dirac-Kaehler equation on the lattice is known to describe the degenerate ''flavours'' appering in Susskind's approach to lattice fermions. We study the modification that has to be made in this equation in order to lift the degeneracy and give the flavours arbitrary different masses. (orig.)

  2. MR findings of degenerating parenchymal neurocysticercosis

    International Nuclear Information System (INIS)

    Lee, Yul; Chung, Eun A; Yang, Ik; Park, Hae Jung; Chung, Soo Young

    1996-01-01

    To evaluate MR imaging findings of degenerating parenchymal neurocysticercosis and to determine the characteristics which distinguish it from other brain diseases. MR imagings of 19 patients (56 lesions) of degenerating parenchymal neurocysticercosis were retrospectively evaluated, focusing on the size and location of lesions signal intensity patterns of cyst fluid and wall, the extent of the surrounding edema and features of contrast enhancement. Degenerating parenchymal neurocysticercosis was located in gray or subcortical while matter in 89.3% of 56 lesions (50/56) ; most of these (98.2%) were smaller than 2 cm in diameter. Cyst fluid signal was hyperintense relative to CSF on T1 and proton density weighted images (92.9%). A hypointense signal rim of the cyst wall was noted in the lesions on proton density (92.9%) and T2 weighted (98.2%) images, Surrounding edema was mostly mild. Peripheral rim enhancement was noted in all lesions, and this was frequently irregular and lobulated (67.9%) with a focal defect in the enhancing rim(41.1%). Findings which could be helpful in distinguishing degenerating parencymal neurocysticercosis from other brain diseases are as follows : small, superficial lesions ; hyperintense signal of the cyst fluid on T1 and proton density weighted images ; hypointense signal of the cyst wall on proton density and T2 weighted images ; relatively mild extent of surrounding edema, and peripheral rim enhancement which is frequently irregular and lobulated with a focal defect in the enhancing rim

  3. Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs

    OpenAIRE

    Lai, Y -L; Chiou, W -Y; Lu, F J; Chiang, L Y

    1999-01-01

    Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin-mediated airway constriction and oxygen radicals, we explored citric acid-induced bronchial constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes+citric acid; hexa(sulphobutyl)fullerenes+phosphoramidon+citric acid; dimethylthiourea (DMTU)+citric acid; and DMTU+phosphoramidon+citric acid. Hexa(sulphobutyl...

  4. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  5. Hippocampal volume and cognitive function in anorexia nervosa.

    Science.gov (United States)

    Connan, Frances; Murphy, Fay; Connor, Steve E J; Rich, Phil; Murphy, Tara; Bara-Carill, Nuria; Landau, Sabine; Krljes, Sanya; Ng, Virginia; Williams, Steve; Morris, Robin G; Campbell, Iain C; Treasure, Janet

    2006-03-31

    We hypothesised that hippocampal volume would be reduced in underweight anorexia nervosa (AN) and associated with impaired hippocampus-dependent cognitive function. Hippocampal and whole brain volumes were measured in 16 women with AN and 16 matched healthy women using magnetic resonance imaging (MRI) and a manual tracing method. Participants also completed the Doors and People Test of hippocampus-dependent memory and an IQ test. After adjustment for total cerebral volume, there was significant bilateral reduction in hippocampal volume in the AN group (8.2% right; 7.5% left). There was no evidence of impaired hippocampus-dependent cognitive function and no evidence of a relationship between hippocampal volume and clinical features of AN. The reduced hippocampal volume in anorexia nervosa is not associated with changes in cognitive function. To understand the cause and consequence of hippocampal size and function, it will be important to integrate endocrine, neuropsychological and neuroimaging studies.

  6. Hippocampal sclerosis and chronic epilepsy following posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Kapina, Viktoria; Vargas, Maria-Isabel; Wohlrab, Gabriele; Vulliemoz, Serge; Fluss, Joel; Seeck, Margitta

    2013-12-01

    Chronic epilepsy has rarely been reported after posterior reversible encephalopathy syndrome (PRES) and the association with hippocampal sclerosis has been suggested only once before. We report the case of a girl admitted at the age of 8 years with idiopathic nephrotic syndrome. On the second day of admission, she presented with focal complex seizures and cerebral MRI showed posterior encephalopathy and no hippocampal sclerosis. MRI after one month confirmed the diagnosis of PRES. The seizures recurred and the girl developed pharmacoresistant epilepsy and was admitted to our hospital for further investigation. Cerebral MRI three years after the diagnosis of PRES showed hippocampal sclerosis which was not present on the initial MRI. We conclude that there is a triggering role of PRES in the development of hippocampal sclerosis. Hippocampal sclerosis may have resulted from seizure-associated damage, alternatively, hypertensive encephalopathy may have led to hippocampal damage via a vascular mechanism.

  7. A Compressed Sensing Perspective of Hippocampal Function

    Directory of Open Access Journals (Sweden)

    Panagiotis ePetrantonakis

    2014-08-01

    Full Text Available Hippocampus is one of the most important information processing units in the brain. Input from the cortex passes through convergent axon pathways to the downstream hippocampal subregions and, after being appropriately processed, is fanned out back to the cortex. Here, we review evidence of the hypothesis that information flow and processing in the hippocampus complies with the principles of Compressed Sensing (CS. The CS theory comprises a mathematical framework that describes how and under which conditions, restricted sampling of information (data set can lead to condensed, yet concise, forms of the initial, subsampled information entity (i.e. of the original data set. In this work, hippocampus related regions and their respective circuitry are presented as a CS-based system whose different components collaborate to realize efficient memory encoding and decoding processes. This proposition introduces a unifying mathematical framework for hippocampal function and opens new avenues for exploring coding and decoding strategies in the brain.

  8. Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

    Directory of Open Access Journals (Sweden)

    Eleni Paizanis

    2007-01-01

    Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

  9. Prediction of dementia by hippocampal shape analysis

    DEFF Research Database (Denmark)

    Achterberg, Hakim C.; van der Lijn, Fedde; den Heijer, Tom

    2010-01-01

    This work investigates the possibility of predicting future onset of dementia in subjects who are cognitively normal, using hippocampal shape and volume information extracted from MRI scans. A group of 47 subjects who were non-demented normal at the time of the MRI acquisition, but were diagnosed...... with dementia during a 9 year follow-up period, was selected from a large population based cohort study. 47 Age and gender matched subjects who stayed cognitively intact were selected from the same cohort study as a control group. The hippocampi were automatically segmented and all segmentations were inspected...... and, if necessary, manually corrected by a trained observer. From this data a statistical model of hippocampal shape was constructed, using an entropy-based particle system. This shape model provided the input for a Support Vector Machine classifier to predict dementia. Cross validation experiments...

  10. Relationships between hippocampal activity and breathing patterns

    DEFF Research Database (Denmark)

    Harper, R M; Poe, G R; Rector, D M

    1998-01-01

    Single cell discharge, EEG activity, and optical changes accompanying alterations in breathing patterns, as well as the knowledge that respiratory musculature is heavily involved in movement and other behavioral acts, implicate hippocampal regions in some aspects of breathing control. The control...... is unlikely to reside in oscillatory breathing movements, because such patterns emerge in preparations retaining only the medulla (and perhaps only the spinal cord). However, momentary changes in breathing patterns induced by affect, startle, whole-body movement changes, or compensatory ventilatory changes...... of hippocampal contributions to breathing control should be viewed in the context that significant interactions exist between blood pressure changes and ventilation, and that modest breathing challenges, such as exposure to hypercapnia or to increased resistive loads, bring into action a vast array of brain...

  11. MR imaging of central nervous system white matter tract degeneration (Wallerian degeneration)

    International Nuclear Information System (INIS)

    Kuhn, M.J.; Johnson, K.A.; Davis, K.R.

    1987-01-01

    Wallerian degeneration is readily demonstrated by MR imaging. Twenty-one patients with MR signal abnormalities in various central nervous system (CNS) white matter tracts were evaluated with regard to (1) nature of signal abnormality, (2) MR anatomy of the involved tract, and (3) primary pathology (e.g., infarct, tumor, hemorrhage). Most examples of wallerian degeneration result in a thin, continuous band of long T1, long T2 signal abnormality conforming to the known anatomic pathway of a CNS axonal tract. Old, large cortical infarcts have the greatest propensity to show subsequent white-matter tract degeneration. Corticospinal tract degeneration is the type most readily visualized, often seen extending completely from the cerebral cortex through the medulla

  12. Ethanol Exposure Causes Muscle Degeneration in Zebrafish

    Directory of Open Access Journals (Sweden)

    Elizabeth C. Coffey

    2018-03-01

    Full Text Available Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA, which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle.

  13. Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

    Science.gov (United States)

    Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

    2016-11-01

    Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Taurine increases hippocampal neurogenesis in aging mice.

    Science.gov (United States)

    Gebara, Elias; Udry, Florian; Sultan, Sébastien; Toni, Nicolas

    2015-05-01

    Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging. Copyright © 2015. Published by Elsevier B.V.

  15. Active sulforhodamine 101 uptake into hippocampal astrocytes.

    Directory of Open Access Journals (Sweden)

    Christian Schnell

    Full Text Available Sulforhodamine 101 (SR101 is widely used as a marker of astrocytes. In this study we investigated labeling of astrocytes by SR101 in acute slices from the ventrolateral medulla and the hippocampus of transgenic mice expressing EGFP under the control of the astrocyte-specific human GFAP promoter. While SR101 efficiently and specifically labeled EGFP-expressing astrocytes in hippocampus, we found that the same staining procedure failed to label astrocytes efficiently in the ventrolateral medulla. Although carbenoxolone is able to decrease the SR101-labeling of astrocytes in the hippocampus, it is unlikely that SR101 is taken up via gap-junction hemichannels because mefloquine, a blocker for pannexin and connexin hemichannels, was unable to prevent SR101-labeling of hippocampal astrocytes. However, SR101-labeling of the hippocampal astrocytes was significantly reduced by substrates of organic anion transport polypeptides, including estron-3-sulfate and dehydroepiandrosterone sulfate, suggesting that SR101 is actively transported into hippocampal astrocytes.

  16. Tuberous sclerosis complex coexistent with hippocampal sclerosis.

    Science.gov (United States)

    Lang, Min; Prayson, Richard A

    2016-02-01

    Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

    Science.gov (United States)

    Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

    2015-08-20

    Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the

  18. Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.

    Directory of Open Access Journals (Sweden)

    Gang Chen

    Full Text Available Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30-50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time. Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM. The expressions of C/EBP homologous protein (CHOP and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P<0.05. The apoptotic neurons were condensed and had clumped chromatin with fragmentation of the nuclear membrane, verifying apoptotic degeneration in the sevoflurane group rats by TEM observation. The expressions of CHOP and caspase-12 increased, and the number of TUNEL positive cells of the hippocampus also increased in the sevoflurane group rats (P<0.05. The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats. The ER stress mediated neurons apoptosis may play a role in the sevoflurane-induced memory impairment in aging rats.

  19. Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

    Science.gov (United States)

    Sahly, I; Bar Nachum, S; Suss-Toby, E; Rom, A; Peretz, A; Kleiman, J; Byk, T; Selinger, Z; Minke, B

    1992-01-01

    Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant. Images PMID:1309615

  20. Early detection of Alzheimer's disease using MRI hippocampal texture

    DEFF Research Database (Denmark)

    Sørensen, Lauge; Igel, Christian; Hansen, Naja Liv

    2016-01-01

    Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change...... in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently...

  1. Mucoid degeneration of the anterior cruciate Ligament: a case report ...

    African Journals Online (AJOL)

    We report a case of mucoid degeneration of the anterior cruciate ligament (ACL). Mucoid degeneration of the ACL is a very rare cause of knee pain. There have been only some reported cases of mucoid degeneration of the ACL in the English literature. We reviewed previous reports and summarized clinical features and ...

  2. Degenerate r-Stirling Numbers and r-Bell Polynomials

    Science.gov (United States)

    Kim, T.; Yao, Y.; Kim, D. S.; Jang, G.-W.

    2018-01-01

    The purpose of this paper is to exploit umbral calculus in order to derive some properties, recurrence relations, and identities related to the degenerate r-Stirling numbers of the second kind and the degenerate r-Bell polynomials. Especially, we will express the degenerate r-Bell polynomials as linear combinations of many well-known families of special polynomials.

  3. Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures

    DEFF Research Database (Denmark)

    Penkowa, Milena; Florit, Sergi; Giralt, Mercedes

    2005-01-01

    We examined metallothionein (MT)-induced neuroprotection during kainic acid (KA)-induced excitotoxicity by studying transgenic mice with MT-I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed by inflammation and delayed brain damage. We show for th...

  4. Retarded hippocampal development following prenatal exposure to ...

    African Journals Online (AJOL)

    Results: Rats in Group A showed no implantation, rats in Group B had abortion on the 7th day after administration, and rats in Group C gave birth with their litters showing retarded hippocampus development and neural degeneration and rats in Group D (control) showed normal development. Conclusion: Ethanolic extract of ...

  5. Heterologous expression of a tannic acid-inducible laccase3 of Cryphonectria parasitica in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Kim Dae-Hyuk

    2010-02-01

    Full Text Available Abstract Background A tannic acid-inducible and mycoviral-regulated laccase3 (lac3 from the chestnut blight fungus Cryphonectria parasitica has recently been identified, but further characterization was hampered because of the precipitation of protein products by tannic acid supplementation. The present study investigated the heterologous expression of the functional laccase3 using a yeast Saccharomyces cerevisiae. Results Laccase activity in the culture broth of transformants measured using a laccase-specific substrate suggested that the lac3 gene was successfully expressed and the corresponding protein product secreted into the culture media. In addition, activity staining and Western blot analysis of a native gel revealed that the enzyme activity co-existed with the protein product specific to anti-laccase3 antibody, confirming that the cloned lac3 gene is responsible for the laccase activity. When transformants were grown on plates containing tannic acid-supplemented media, brown coloration was observed around transformed cells, indicating the oxidation of tannic acid. However, the enzymatic activity was measurable only in the selective ura- media and was negligible in nonselective nutrient-rich culture conditions. This was in part because of the increased plasmid instability in the nonselective media. Moreover, the protein product of lac3 appears to be sensitive to the cultured nonselective nutrient-rich broth, because a rapid decline in enzymatic activity was observed when the cultured broth of ura- media was mixed with that of nonselective nutrient-rich broth. In addition, constitutive expression of the lac3 gene resulted in a reduced cell number of the lac3 transformants compared to that of vector-only transformed control. However, the presence of recombinant vector without lac3 induction did not affect the growth of transformants. Conclusions The results suggest that expression of the lac3 gene has an inhibitory effect on the growth of

  6. Apathy in corticobasal degeneration: possible parietal involvement.

    Science.gov (United States)

    Moretti, Rita; Caberlotto, R; Signori, R

    Corticobasal degeneration is a rare disorder, which usually consists of a combination of complex movement disorders, apraxia and cortical changes. Its definition is still evolving and in 2013 an international consortium tried to develop new criteria, based on a systematic literature review. Over a long period of time, we carefully selected 23 patients who fulfilled the criteria for a diagnosis of corticobasal degeneration; all had the so-called corticobasal syndrome phenotype, in accordance with Armstrong et al. (2013). Through a dedicated study, we set out to study behavioral alterations, specifically apathy, and to compare the results obtained with those deriving from a well-defined Parkinson's disease population. On the basis of our limited but specific results, we argue for a possible role of the parietal neural networks as a determinant of apathy, and provide an overview of emerging data in the imaging and pathology literature.

  7. Inflammation in intervertebral disc degeneration and regeneration

    Science.gov (United States)

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  8. Degenerate odd Poisson bracket on Grassmann variables

    International Nuclear Information System (INIS)

    Soroka, V.A.

    2000-01-01

    A linear degenerate odd Poisson bracket (antibracket) realized solely on Grassmann variables is proposed. It is revealed that this bracket has at once three Grassmann-odd nilpotent Δ-like differential operators of the first, second and third orders with respect to the Grassmann derivatives. It is shown that these Δ-like operators, together with the Grassmann-odd nilpotent Casimir function of this bracket, form a finite-dimensional Lie superalgebra

  9. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac

    2012-12-01

    Full Text Available This paper introduces the theory of channel modeling for positioning applications in UHF RFID. It explains basic parameters for channel characterization from both the narrowband and wideband point of view. More details are given about ranging and direction finding. Finally, several positioning scenarios are analyzed with developed channel models. All the described models use a degenerate channel, i.e. combined signal propagation from the transmitter to the tag and from the tag to the receiver.

  10. Molecular markers for granulovacuolar degeneration are present in rimmed vacuoles.

    Directory of Open Access Journals (Sweden)

    Masahiro Nakamori

    Full Text Available BACKGROUND: Rimmed vacuoles (RVs are round-oval cytoplasmic inclusions, detected in muscle cells of patients with myopathies, such as inclusion body myositis (IBM and distal myopathy with RVs (DMRV. Granulovacuolar degeneration (GVD bodies are spherical vacuoles containing argentophilic and hematoxyphilic granules, and are one of the pathological hallmarks commonly found in hippocampal pyramidal neurons of patients with aging-related neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. These diseases are common in the elderly and share some pathological features. Therefore, we hypothesized that mechanisms of vacuolar formation in RVs and GVD bodies are common despite their role in two differing pathologies. We explored the components of RVs by immunohistochemistry, using antibodies for GVD markers. METHODS: Subjects included one AD case, eight cases of sporadic IBM, and three cases of DMRV. We compared immunoreactivity and staining patterns for GVD markers. These markers included: (1 tau-modifying proteins (caspase 3, cyclin-dependent kinase 5 [CDK5], casein kinase 1δ [CK1δ], and c-jun N-terminal kinase [JNK], (2 lipid raft-associated materials (annexin 2, leucine-rich repeat kinase 2 [LRRK2], and flotillin-1, and (3 other markers (charged multi-vesicular body protein 2B [CHMP2B] and phosphorylated transactive response DNA binding protein-43 [pTDP43] in both GVD bodies and RVs. Furthermore, we performed double staining of each GVD marker with pTDP43 to verify the co-localization. RESULTS: GVD markers, including lipid raft-associated proteins and tau kinases, were detected in RVs. CHMP2B, pTDP43, caspase 3, LRRK2, annexin 2 and flotillin-1 were detected on the rim and were diffusely distributed in the cytoplasm of RV-positive fibers. CDK5, CK1δ and JNK were detected only on the rim. In double staining experiments, all GVD markers colocalized with pTDP43 in RVs. CONCLUSIONS: These results suggest that RVs of muscle

  11. Can Neutrinos be Degenerate in Mass?

    CERN Document Server

    Ellis, Jonathan Richard; Ellis, John; Lola, Smaragda

    1999-01-01

    We reconsider the possibility that the masses of the three light neutrinos of the Standard Model might be almost degenerate and close to the present upper limits from Tritium beta decay and cosmology. In such a scenario, the cancellations required by the latest upper limit on neutrinoless double-beta decay enforce near-maximal mixing that may be compatible only with the vacuum-oscillation scenario for solar neutrinos. We argue that the mixing angles yielded by degenerate neutrino mass-matrix textures are not in general stable under small perturbations. We evaluate within the MSSM the generation-dependent one-loop renormalization of neutrino mass-matrix textures that yielded degenerate masses and large mixing at the tree level. We find that m_{nu_e} > m_{nu_mu} > m_{nu_tau} after renormalization, excluding MSW effects on solar neutrinos. We verify that bimaximal mixing is not stable, and show that the renormalized masses and mixing angles are not compatible with all the experimental constraints, even for tanbe...

  12. Automatic calculation of hippocampal atrophy rates using a hippocampal template and the boundary shift integral.

    Science.gov (United States)

    Barnes, J; Boyes, R G; Lewis, E B; Schott, J M; Frost, C; Scahill, R I; Fox, N C

    2007-11-01

    We describe a method of automatically calculating hippocampal atrophy rates on T1-weighted MR images without manual delineation of hippocampi. This method was applied to a group of Alzheimer's disease (AD) (n=36) and control (n=19) subjects and compared with manual methods (manual segmentation of baseline and repeat-image hippocampi) and semi-automated methods (manual segmentation of baseline hippocampi only). In controls, mean (S.D.) atrophy rates for manual, semi-automated, and automated methods were 18.1 (53.5), 15.3 (50.2) and 11.3 (50.4) mm3 loss per year, respectively. In AD patients these rates were 174.6 (106.5) 159.4 (101.2) and 172.1 (123.1) mm3 loss per year, respectively. The automated method was a significant predictor of disease (p=0.001) and gave similar group discrimination compared with both semi-automated and manual methods. The automated hippocampal analysis in this small study took approximately 20 min per hippocampal pair on a 3.4 GHz Intel Xeon server, whereas manual delineation of each hippocampal pair took approximately 90 min of operator-intensive labour. This method may be useful diagnostically or in studies where analysis of many scans may be required.

  13. Hippocampal EEG and behaviour in dog. I. Hippocampal EEG correlates of gross motor behaviour

    NARCIS (Netherlands)

    Arnolds, D.E.A.T.; Lopes da Silva, F.H.; Aitink, J.W.; Kamp, A.

    It was shown that rewarding spectral shifts (i.e. increase in amplitude or peak frequency of the hippocampal EEG) causes a solitary dog to show increased motor behaviour. Rewarded spectral shifts concurred with a variety of behavioural transitions. It was found that statistically significant

  14. Localized gene transfer into organotypic hippocampal slice cultures and acute hippocampal slices

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Shen, H

    1993-01-01

    Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and express genes into fully differentiated, post-mitotic neurons. These vectors also transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter quantities of a virus stock of HSVlac, an HSV vector...

  15. Regional hippocampal involvement and cognitive impairment in pediatric multiple sclerosis.

    Science.gov (United States)

    Rocca, Maria A; Morelli, Maria E; Amato, Maria P; Moiola, Lucia; Ghezzi, Angelo; Veggiotti, Pierangelo; Capra, Ruggero; Pagani, Elisabetta; Portaccio, Emilio; Fiorino, Agnese; Pippolo, Lorena; Pera, Maria C; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2016-04-01

    We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired (n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests. © The Author(s), 2015.

  16. The Impact of Sleep Loss on Hippocampal Function

    Science.gov (United States)

    Prince, Toni-Moi; Abel, Ted

    2013-01-01

    Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep…

  17. Degenerate pressure driven modified nucleus-acoustic waves in degenerate plasmas

    Science.gov (United States)

    Mamun, A. A.

    2018-02-01

    The existence of degenerate pressure driven modified nucleus-acoustic (DPDMNA) waves propagating in a cold degenerate quantum plasma (DQP) system [containing cold inertialess degenerate electron species (DES), cold inertial non-degenerate light nucleus species (LNS), and stationary heavy nucleus species (HNS)] is predicted for the first time. The DPDMNA waves (in which the mass density of the cold LNS provides the inertia and the cold inertialess DES gives rise to the restoring force) are new since they completely disappear if the degenerate pressure of the cold DES is neglected. It is found that the phase speed (Vp) of the DPDMNA waves decreases with the rise of the charge number density of the stationary HNS for both non-relativistic and ultra-relativistic DES, and that the ultra-relativistic DES does not have any effect on Vp when β = 1, where β = Λc/Λe with Λ e = ne 0 - 1 / 3 being the average inter-electron distance in the DQP system and Λc being the constant (˜10-10 cm) for the DES. However, the ultra-relativistic DES does have quite a significant effect on Vp for β ≫ 1 and β ≪ 1, and the ultra-relativistic effect significantly enhances (reduces) Vp for β ≫ 1 (β ≪ 1). The DPDMNA waves and their dispersion properties are expected to be useful in understanding the basic features of the electrostatic perturbation mode in space and laboratory DQP systems.

  18. Impaired retention of spatial memory after transection of longitudinally oriented axons of hippocampal CA3 pyramidal cells

    Science.gov (United States)

    Steffenach, Hill-Aina; Sloviter, Robert S.; Moser, Edvard I.; Moser, May-Britt

    2002-03-01

    Longitudinally oriented axon collaterals of CA3 pyramidal cells may be critical for integrating distributed information in the hippocampus. To investigate the possible role of this pathway in the retention of spatial memory, we made a single transversely oriented cut through the dorsal CA3 region of each hippocampus. Although the lesion involved water maze in preoperatively trained rats. New learning in a different water maze was attenuated. No significant impairment occurred in rats with longitudinally oriented cuts, or in animals with ibotenic acid-induced lesions of similar magnitude. To characterize the effect of a focal lesion on the integrity of longitudinally projecting axons, we stained degenerating cells and fibers in rats with unilateral CA3 transections by using FluoroJade-B. Degenerating terminals were seen across a wide region posterior to the cut, and were present in the strata of areas CA3 and CA1 that are innervated by CA3 pyramidal cells. These results suggest that the integrity of longitudinally oriented, translamellar axons of CA3 pyramidal cells may be necessary for efficient acquisition and retention of spatial memory.

  19. Triheteromeric NMDA Receptors at Hippocampal Synapses

    Science.gov (United States)

    Tovar, Kenneth R.; McGinley, Matthew J.; Westbrook, Gary L.

    2013-01-01

    NMDA receptors are composed of two GluN1 (N1) and two GluN2 (N2) subunits. Constituent N2 subunits control the pharmacological and kinetic characteristics of the receptor. NMDA receptors in hippocampal or cortical neurons are often thought of as diheteromeric, i.e., containing only one type of N2 subunit. However, triheteromeric receptors with more than one type of N2 subunit also have been reported and the relative contribution of di- and triheteromeric NMDA receptors at synapses has been difficult to assess. Because wild-type hippocampal principal neurons express N1, N2A and N2B, we used cultured hippocampal principal neurons from N2A and N2B-knockout mice as templates for diheteromeric synaptic receptors. Summation of N1/N2B and N1/N2A excitatory postsynaptic currents could not account for the deactivation kinetics of wild-type excitatory postsynaptic currents (EPSCs) however. To make a quantitative estimate of NMDA receptor subtypes at wild-type synapses, we used the deactivation kinetics, as well as the effects of the competitive antagonist NVP-AAM077. Our results indicate that three types of NMDA receptors contribute to the wild-type EPSC, with at least two-thirds being triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors revealed deactivation kinetics and pharmacology distinct from either diheteromeric receptor subtype. Because of differences in open probability, synaptic triheteromeric receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to 1. Our results suggest that triheteromeric NMDA receptors must be either preferentially assembled or preferentially localized at synapses. PMID:23699525

  20. Physical exercise induces hippocampal neurogenesis and prevents cognitive decline.

    Science.gov (United States)

    Ma, Chun-Lian; Ma, Xiao-Tang; Wang, Jin-Ju; Liu, Hua; Chen, Yan-Fang; Yang, Yi

    2017-01-15

    Accumulating evidence from animal and human research indicate that adult hippocampal neurogenesis plays a key role in cognition. Meanwhile, cognitive decline is well known to associate with ageing-related neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore, prevention of hippocampal neurogenesis reduction should be critical for these diseases. Physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential therapy or an adjunctive therapeutic strategy for cognitive decline. In this review, we discuss the recent findings on hippocampal neurogenesis and the incorporation of new born neurons into the neuronal network in humans and in rodents. By focusing on hippocampal neurogenesis, we illustrate the role and possible mechanisms of physical exercise in cognition preservation. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Hippocampal “Time Cells”: Time versus Path Integration

    Science.gov (United States)

    Kraus, Benjamin J.; Robinson, Robert J.; White, John A.; Eichenbaum, Howard; Hasselmo, Michael E.

    2014-01-01

    SUMMARY Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in place on a treadmill, thus “clamping” behavior and location, while we varied the treadmill speed to distinguish time elapsed from distance traveled. Hippocampal neurons were strongly influenced by time and distance, and less so by minor variations in location. Furthermore, the activity of different neurons reflected integration over time and distance to varying extents, with most neurons strongly influenced by both factors and some significantly influenced by only time or distance. Thus, hippocampal neuronal networks captured both the organization of time and distance in a situation where these dimensions dominated an ongoing experience. PMID:23707613

  2. Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats.

    Science.gov (United States)

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2011-02-04

    Huntington disease is a neurodegenerative disease with complex pathophysiology. Recently, role of neuroinflammation and interplay between various other cellular cascades have been suggested to be involved in pathophysiology of Huntington disease. Involvement of calcium overload mediated oxidative damage and excitotoxicity have been suggested to play a central role in quinolinic acid induced Huntington like symptoms. The present study has been carried out to investigate the neuroprotective effect of calcium channel blockers (verapamil and diltiazem) against quinolinic acid induced dysfunction in motor, biochemical and neuroinflammatory signaling in rats. Intrastriatal quinolinic acid administration leads to significant motor [locomotor (72% reduction), rotarod (55% reduction), balance beam walk performance] dysfunction coupled with the marked oxidative damage and increased neuroinflammatory markers [TNF-α (140%), IL-6 (115%), caspase-3(75%)] levels in striatum as compared to the sham treatment. Verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) drug treatment for 21days resulted in a significant improvement in the motor function (improvement in locomotor activity, rotarod and balance beam walk performance). Further, verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) treatment significantly attenuated oxidative damage, level of proinflammatory mediators (TNF-α IL-6 and caspase-3) in quinolinic acid treated animals. Results of the present study demonstrate that protective effect of these calcium channel blockers (verapamil, diltiazem) might be due to their inhibitory action on different neuroinflammatory pathways against quinolinic acid induced Huntington disease like symptoms in rats. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways.

    Science.gov (United States)

    Chen, Bi; Cai, Hou-Rong; Xue, Shan; You, Wen-Jie; Liu, Bin; Jiang, Han-Dong

    2016-08-01

    The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-β/Smad3 signaling was also involved in the bile acid-induced EMT and lung fibroblast differentiation. Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways. © 2016 Asian Pacific Society of Respirology.

  4. [Effects of sleep deprivation in hippocampal neurogenesis].

    Science.gov (United States)

    López-Virgen, Verónica; Zárate-López, David; Adirsch, Fabián L; Collas-Aguilar, Jorge; González-Pérez, Óscar

    2015-01-01

    Adult neurogenesis in the dentate gyrus (DG) in the hippocampus is a process that involves proliferation, differentiation, maturation, migration, and integration of young neurons in the granular layer of DG. These newborn neurons mature in three to four weeks and incorporate into neural circuits in the hippocampus. There, these new neurons play a role in cognitive functions, such as acquisition and retention of memory, which are consolidated during sleep period. In this review, we describe recent findings that associate sleep deprivation with changes in hippocampal neurogenesis and cognitive processes. In addition, we describe possible mechanisms implicated in this deterioration such as circadian rhythm, melatonin receptors, and growth factors.

  5. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    Science.gov (United States)

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and

  6. Aerobic fitness, hippocampal viscoelasticity, and relational memory performance.

    Science.gov (United States)

    Schwarb, Hillary; Johnson, Curtis L; Daugherty, Ana M; Hillman, Charles H; Kramer, Arthur F; Cohen, Neal J; Barbey, Aron K

    2017-06-01

    The positive relationship between hippocampal structure, aerobic fitness, and memory performance is often observed among children and older adults; but evidence of this relationship among young adults, for whom the hippocampus is neither developing nor atrophying, is less consistent. Studies have typically relied on hippocampal volumetry (a gross proxy of tissue composition) to assess individual differences in hippocampal structure. While volume is not specific to microstructural tissue characteristics, microstructural differences in hippocampal integrity may exist even among healthy young adults when volumetric differences are not diagnostic of tissue health or cognitive function. Magnetic resonance elastography (MRE) is an emerging noninvasive imaging technique for measuring viscoelastic tissue properties and provides quantitative measures of tissue integrity. We have previously demonstrated that individual differences in hippocampal viscoelasticity are related to performance on a relational memory task; however, little is known about health correlates to this novel measure. In the current study, we investigated the relationship between hippocampal viscoelasticity and cardiovascular health, and their mutual effect on relational memory in a group of healthy young adults (N=51). We replicated our previous finding that hippocampal viscoelasticity correlates with relational memory performance. We extend this work by demonstrating that better aerobic fitness, as measured by VO 2 max, was associated with hippocampal viscoelasticity that mediated the benefits of fitness on memory function. Hippocampal volume, however, did not account for individual differences in memory. Therefore, these data suggest that hippocampal viscoelasticity may provide a more sensitive measure to microstructural tissue organization and its consequences to cognition among healthy young adults. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Alzheimer's Disease Diagnostic Performance of a Multi-Atlas Hippocampal Segmentation Method using the Harmonized Hippocampal Protocol

    DEFF Research Database (Denmark)

    Anker, Cecilie Benedicte; Sørensen, Lauge; Pai, Akshay

    PURPOSE Hippocampal volumetry is the most widely used structural MRI biomarker of Alzheimer’s disease (AD), and state-of-the-art, automatic hippocampal segmentation can be obtained using longitudinal FreeSurfer. In this study, we compare the diagnostic AD performance of a single time point, multi...

  8. Proteomic Analysis of the Effect of Acupuncture on the Suppression of Kainic Acid-Induced Neuronal Destruction in Mouse Hippocampus

    OpenAIRE

    Bae, Chang-Hwan; Kim, Dong-Soo; Jun, Ye Lee; Kwon, Sunoh; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2013-01-01

    Kainic acid (KA) is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20–25 g) received acupuncture treatment at HT8 acupoint bilaterally once a day for 3...

  9. Patterns of Microglial Cell Activation in Alzheimer Disease and Frontotemporal Lobar Degeneration.

    Science.gov (United States)

    Taipa, Ricardo; Brochado, Paulo; Robinson, Andrew; Reis, Inês; Costa, Patrício; Mann, David M; Melo Pires, Manuel; Sousa, Nuno

    2017-01-01

    Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. In this study, we sought to characterize the distribution of microglial cell activation in 2 neurodegenerative dementias with distinct protein signatures, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to determine if there was an anatomical correlation with the phenotypes most commonly associated with these conditions. The distribution and extent of microglial cell activation was assessed semiquantitatively in the hippocampal formation, cortical gray matter, and subcortical white matter of CD68-immunostained sections of the frontal, temporal, parietal, and occipital cortices from 15 pathologically confirmed cases of AD, 13 cases of FTLD, and 18 controls. Significantly higher levels of microglial cell activation occurred in the subiculum in AD and FTLD than in controls. Additionally, AD had higher microglial activation in the CA1 and FTLD in the hippocampal white matter than the controls. Microglial activation was greater in the dentate gyrus molecular layer in AD than in FTLD. In the cortical regions, the 2 pathological groups differed only in frontal white matter, with the FTLD group showing higher microglial scores. FTLD showed higher microglial activation in the white matter compared to the respective gray matter in the entorhinal, temporal, and frontal regions. Our work expands the knowledge of the distribution and magnitude of microglial activation in these disorders. Additionally, we found some microglial circuit-specific patterns that could help to explain some of the clinical overlap between AD and FTLD-TDP, namely in memory deficits. © 2017 S. Karger AG, Basel.

  10. Can Molecular Hippocampal Alterations Explain Behavioral ...

    Science.gov (United States)

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

  11. Acetic acid induces Sch9p-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria.

    Science.gov (United States)

    Rego, António; Cooper, Katrina F; Snider, Justin; Hannun, Yusuf A; Costa, Vítor; Côrte-Real, Manuela; Chaves, Susana R

    2018-02-27

    Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1∆ mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 deletion leads to a higher retention of Isc1p in the endoplasmic reticulum upon acetic acid exposure. We also found that the higher resistance of all mutants correlates with higher levels of endogenous mitochondrial phosphorylated long chain bases (LCBPs), suggesting that changing the sphingolipid balance in favour of LCBPs in mitochondria results in increased survival to acetic acid. In conclusion, our results suggest that Sch9p pathways modulate acetic acid-induced cell death, through the regulation of Isc1p cellular distribution, thus affecting the sphingolipid balance that regulates cell fate. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1.

    Science.gov (United States)

    Shah, Bhavik P; Liu, Pin; Yu, Tian; Hansen, Dane R; Gilbertson, Timothy A

    2012-01-01

    Fatty acid-induced stimulation of enteroendocrine cells leads to release of the hormones such as cholecystokinin (CCK) that contribute to satiety. Recently, the fatty acid activated G protein-coupled receptor GPR120 has been shown to mediate long-chain unsaturated free fatty acid-induced CCK release from the enteroendocrine cell line, STC-1, yet the downstream signaling pathway remains unclear. Here we show that linoleic acid (LA) elicits membrane depolarization and an intracellular calcium rise in STC-1 cells and that these responses are significantly reduced when activity of G proteins or phospholipase C is blocked. LA leads to activation of monovalent cation-specific transient receptor potential channel type M5 (TRPM5) in STC-1 cells. LA-induced TRPM5 currents are significantly reduced when expression of TRPM5 or GPR120 is reduced using RNA interference. Furthermore, the LA-induced rise in intracellular calcium and CCK secretion is greatly diminished when expression of TRPM5 channels is reduced using RNA interference, consistent with a role of TRPM5 in LA-induced CCK secretion in STC-1 cells.

  13. Neurotoxicity of coral snake phospholipases A2 in cultured rat hippocampal neurons.

    Science.gov (United States)

    de Carvalho, Nathalia Delazeri; Garcia, Raphael CaioTamborelli; Ferreira, Adilson Kleber; Batista, Daniel Rodrigo; Cassola, Antonio Carlos; Maria, Durvanei; Lebrun, Ivo; Carneiro, Sylvia Mendes; Afeche, Solange Castro; Marcourakis, Tania; Sandoval, Maria Regina Lopes

    2014-03-13

    The neurotoxicity of two secreted Phospholipases A2 from Brazilian coral snake venom in rat primary hippocampal cell culture was investigated. Following exposure to Mlx-8 or Mlx-9 toxins, an increase in free cytosolic Ca(2+) and a reduction in mitochondrial transmembrane potential (ΔΨm) became evident and occurred prior to the morphological changes and cytotoxicity. Exposure of hippocampal neurons to Mlx-8 or Mlx-9 caused a decrease in the cell viability as assessed by MTT and LDH assays. Inspection using fluorescent images and ultrastructural analysis by scanning and transmission electron microscopy showed that multiphase injury is characterized by overlapping cell death phenotypes. Shrinkage, membrane blebbing, chromatin condensation, nucleosomal DNA fragmentation and the formation of apoptotic bodies were observed. The most striking alteration observed in the electron microscopy was the fragmentation and rarefaction of the neuron processes network. Degenerated terminal synapses, cell debris and apoptotic bodies were observed among the fragmented fibers. Numerous large vacuoles as well as swollen mitochondria and dilated Golgi were noted. Necrotic signs such as a large amount of cellular debris and membrane fragmentation were observed mainly when the cells were exposed to highest concentration of the PLA2-neurotoxins. PLA2s exposed cultures showed cytoplasmic vacuoles filled with cell debris, clusters of mitochondria presented mitophagy-like structures that are in accordance to patterns of programmed cell death by autophagy. Finally, we demonstrated that the sPLA2s, Mlx-8 and Mlx-9, isolated from the Micrurus lemniscatus snake venom induce a hybrid cell death with apoptotic, autophagic and necrotic features. Furthermore, this study suggests that the augment in free cytosolic Ca(2+) and mitochondrial dysfunction are involved in the neurotoxicity of Elapid coral snake venom sPLA2s. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Activation of neural stem cells from quiescence drives reactive hippocampal neurogenesis after alcohol dependence.

    Science.gov (United States)

    Hayes, Dayna M; Nickell, Chelsea G; Chen, Kevin Y; McClain, Justin A; Heath, Megan M; Deeny, M Ayumi; Nixon, Kimberly

    2018-05-01

    Neural stem cell-driven adult neurogenesis contributes to the integrity of the hippocampus. Excessive alcohol consumption in alcoholism results in hippocampal degeneration that may recover with abstinence. Reactive, increased adult neurogenesis during abstinence following alcohol dependence may contribute to recovery, but the mechanism driving reactive neurogenesis is not known. Therefore, adult, male rats were exposed to alcohol for four days and various markers were used to examine cell cycle dynamics, the percentage and number of neural progenitor cell subtypes, and the percentage of quiescent versus activated progenitors. Using a screen for cell cycle perturbation, we showed that the cell cycle is not likely altered at 7 days in abstinence. As the vast majority of Bromodeoxyuridine-positive (+) cells were co-labeled with progenitor cell marker, Sox2, we then developed a quadruple fluorescent labeling scheme to examine Type-1, -2a, -2b and -3 progenitor cells simultaneously. Prior alcohol dependence indiscriminately increased all subtypes at 7 days, the peak of the reactive proliferation. An evaluation of the time course of reactive cell proliferation revealed that cells begin proliferating at 5 days post alcohol, where only actively dividing Type 2 progenitors were increased by alcohol. Furthermore, prior alcohol increased the percentage of actively dividing Sox2+ progenitors, which supported that reactive neurogenesis is likely due to the activation of progenitors out of quiescence. These observations were associated with granule cell number returning to normal at 28 days. Therefore, activating stem and progenitor cells out of quiescence may be the mechanism underlying hippocampal recovery in abstinence following alcohol dependence. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Aneutronic Fusion in a Degenerate Plasma

    International Nuclear Information System (INIS)

    Son, S.; Fisch, N.J.

    2004-01-01

    In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot

  16. Malignant degeneration in neurofibromatosis: 3 case report

    International Nuclear Information System (INIS)

    Lee, Jong Moon; Kang, Eun Young; Lee, Nam Joon; Chung, Kyoo Byung; Suh, Won Hyuck

    1989-01-01

    Von Recklinghausen's nuerofilbromatosis is a kind of neurocutaneous syndrome characterized by skin, nervous system, neuromusculoskeletal manifestations. Most central and peripheral nervous neoplastic lesions in neurofibromatosis are benign but have a significant potential for malignant transformation such as neurofibrosarcoma, neurogenic sarcoma, malignant schwannoma. And it is relatively common disorder but malignant change with radiologic findings has been reported rarely in Korea. Recently we experienced three cases of malignant degeneration in neurofibromatosis and confirmed by pathology. So we report the cases with review including radiologic findings

  17. Aneutronic Fusion in a Degenerate Plasma

    Energy Technology Data Exchange (ETDEWEB)

    S. Son; N.J. Fisch

    2004-09-03

    In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot.

  18. Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats.

    Science.gov (United States)

    Li, Hui; Liu, Yi; Lin, Li-Ting; Wang, Xue-Rui; Du, Si-Qi; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Liu, Cun-Zhi

    2016-01-01

    Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  20. MRI and MR tractography in bilateral hypertrophic olivary degeneration

    International Nuclear Information System (INIS)

    Sen, Debraj; Gulati, Yoginder S.; Malik, Virender; Mohimen, Aneesh; Sibi, Eranki; Reddy, Deepak Chandra

    2014-01-01

    Hypertrophic olivary degeneration is a trans-synaptic neuronal degeneration associated with hypertrophy of the inferior olivary nucleus due to a lesion in the triangle of Guillain-Mollaret. Familiarity with this entity on magnetic resonance imaging (MRI) is essential to avoid other erroneous ominous diagnoses. We present a case of bilateral hypertrophic olivary degeneration and discuss the etiopathogenesis and MRI findings in this entity. The contributory role of MR tractography in the diagnosis is also highlighted

  1. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    OpenAIRE

    Mathew, David J.; Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were al...

  2. Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson's disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory function when cultured in spheroids.

    Science.gov (United States)

    Berg, Jürgen; Roch, Manfred; Altschüler, Jennifer; Winter, Christine; Schwerk, Anne; Kurtz, Andreas; Steiner, Barbara

    2015-02-01

    Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson's disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype.

  3. Hippocampal sclerosis: correlation of MR imaging findings with surgical outcome

    International Nuclear Information System (INIS)

    Kim, Yoon Hee; Chang, Kee Hyun; Kim, Kyung Won; Han, Moon Hee; Park, Sung Ho; Nam, Hyun Woo; Choi, Kyu Ho; Cho, Woo Ho

    2001-01-01

    Atrophy and a high T2 signal of the hippocampus are known to be the principal MR imaging findings of hippocampal sclerosis. The purpose of this study was to determine whether or not individual MRI findings correlate with surgical outcome in patients with this condition. Preoperative MR imaging findings in 57 consecutive patients with pathologically-proven hippocampal sclerosis who underwent anterior temporal lobectomy and were followed-up for 24 months or more were retrospectively reviewed, and the results were compared with the postsurgical outcome (Engel classification). The MR images included routine sagittal T1-weighted and axial T2-weighted spin-echo images, and oblique coronal T1-weighted 3D gradient-echo and T2-weighted 2D fast spin-echo images obtained on either a 1.5 T or 1.0 T unit. The images were visually evaluated by two neuroradiologists blinded to the outcome; their focus was the presence or absence of atrophy and a high T2 hippocampal signal. Hippocampal atrophy was seen in 96% of cases (55/57) [100% (53/53) of the good outcome group (Engel class I and II), and 50% (2/4) of the poor outcome group (class III and IV)]. A high T2 hippocampal signal was seen in 61% of cases (35/57) [62% (33/53) of the good outcome group and 50% (2/4) of the poor outcome group]. All 35 patients with a high T2 signal had hippocampal atrophy. 'Normal' hippocampus, as revealed by MR imaging, occurred in 4% of patients (2/57), both of whom showed a poor outcome (Engel class III). The presence or absence of hippocampal atrophy correlated well with surgical outcome (p 0.05). Compared with a high T2 hippocampal signal, hippocampal atrophy is more common and correlates better with surgical outcome. For the prediction of this, it thus appears to be the more useful indicator

  4. Towards new treatment strategies for intervertebral disc degeneration : Pathophysiology, histological and biochemical changes in IVD degeneration

    NARCIS (Netherlands)

    Rutges, J.P.H.J.

    2014-01-01

    Approximately 70% to 80% of all people worldwide will experience low back at any moment in their life. Intervertebral disc degeneration is an important cause of chronic low back pain. In most cases chronic low back pain can be treated conservatively with physiotherapy and analgesia. However, in some

  5. Family-Specific Degenerate Primer Design: A Tool to Design Consensus Degenerated Oligonucleotides

    Science.gov (United States)

    Goñi, Sandra Elizabeth; Lozano, Mario Enrique

    2013-01-01

    Designing degenerate PCR primers for templates of unknown nucleotide sequence may be a very difficult task. In this paper, we present a new method to design degenerate primers, implemented in family-specific degenerate primer design (FAS-DPD) computer software, for which the starting point is a multiple alignment of related amino acids or nucleotide sequences. To assess their efficiency, four different genome collections were used, covering a wide range of genomic lengths: Arenavirus (10 × 104 nucleotides), Baculovirus (0.9 × 105 to 1.8 × 105 bp), Lactobacillus sp. (1 × 106 to 2 × 106 bp), and Pseudomonas sp. (4 × 106 to 7 × 106 bp). In each case, FAS-DPD designed primers were tested computationally to measure specificity. Designed primers for Arenavirus and Baculovirus were tested experimentally. The method presented here is useful for designing degenerate primers on collections of related protein sequences, allowing detection of new family members. PMID:23533783

  6. The prognosis of retinal detachment due to lattice degeneration.

    Science.gov (United States)

    Benson, W E; Morse, P H

    1978-09-01

    In a series of 553 consecutive retinal detachments, 29% (120) were due to lattice degeneration. Forty-five percent of these were due to atrophic holes in the lattice degeneration and 55% were due to tears caused by traction posterior to or at the end of a patch of lattice. In phakic patients, retinal detachments due to atrophic holes were most common in young myopes. Detachments due to traction tears were seen in older, less myopic patients. The incidence of massive periretinal proliferation was less (5%) in detachments due to lattice degeneration than in detachments not due to lattice degeneration (6.5%).

  7. Many-Body Green Function of Degenerate Systems

    International Nuclear Information System (INIS)

    Brouder, Christian; Panati, Gianluca; Stoltz, Gabriel

    2009-01-01

    A rigorous nonperturbative adiabatic approximation of the evolution operator in the many-body physics of degenerate systems is derived. This approximation is used to solve the long-standing problem of the choice of the initial states of H 0 leading to eigenstates of H 0 +V for degenerate systems. These initial states are eigenstates of P 0 VP 0 , where P 0 is the projection onto a degenerate eigenspace of H 0 . This result is used to give the proper definition of the Green function, the statistical Green function and the nonequilibrium Green function of degenerate systems. The convergence of these Green functions is established.

  8. Schizophrenia polygenic risk score predicts mnemonic hippocampal activity.

    Science.gov (United States)

    Chen, Qiang; Ursini, Gianluca; Romer, Adrienne L; Knodt, Annchen R; Mezeivtch, Karleigh; Xiao, Ena; Pergola, Giulio; Blasi, Giuseppe; Straub, Richard E; Callicott, Joseph H; Berman, Karen F; Hariri, Ahmad R; Bertolino, Alessandro; Mattay, Venkata S; Weinberger, Daniel R

    2018-02-03

    The use of polygenic risk scores has become a practical translational approach to investigating the complex genetic architecture of schizophrenia, but the link between polygenic risk scores and pathophysiological components of this disorder has been the subject of limited research. We investigated in healthy volunteers whether schizophrenia polygenic risk score predicts hippocampal activity during simple memory encoding, which has been proposed as a risk-associated intermediate phenotype of schizophrenia. We analysed the relationship between polygenic risk scores and hippocampal activity in a discovery sample of 191 unrelated healthy volunteers from the USA and in two independent replication samples of 76 and 137 healthy unrelated participants from Europe and the USA, respectively. Polygenic risk scores for each individual were calculated as the sum of the imputation probability of reference alleles weighted by the natural log of odds ratio from the recent schizophrenia genome-wide association study. We examined hippocampal activity during simple memory encoding of novel visual stimuli assessed using blood oxygen level-dependent functional MRI. Polygenic risk scores were significantly associated with hippocampal activity in the discovery sample [P = 0.016, family-wise error (FWE) corrected within Anatomical Automatic Labeling (AAL) bilateral hippocampal-parahippocampal mask] and in both replication samples (P = 0.033, FWE corrected within AAL right posterior hippocampal-parahippocampal mask in Bari sample, and P = 0.002 uncorrected in the Duke Neurogenetics Study sample). The relationship between polygenic risk scores and hippocampal activity was consistently negative, i.e. lower hippocampal activity in individuals with higher polygenic risk scores, consistent with previous studies reporting decreased hippocampal-parahippocampal activity during declarative memory tasks in patients with schizophrenia and in their healthy siblings. Polygenic risk scores accounted for

  9. Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel.

    Science.gov (United States)

    Dinkelacker, Vera; Valabregue, Romain; Thivard, Lionel; Lehéricy, Stéphane; Baulac, Michel; Samson, Séverine; Dupont, Sophie

    2015-08-01

    Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function. A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory. We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing. We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus

  10. Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions.

    Science.gov (United States)

    Arnold, S E; Franz, B R; Gur, R C; Gur, R E; Shapiro, R M; Moberg, P J; Trojanowski, J Q

    1995-05-01

    The goal of this study was to characterize the hippocampal formation in patients with schizophrenia by measuring neuron density, neuron size, and variability of neuronal axis orientation. Brain tissue was obtained at autopsy from 14 prospectively accrued elderly patients with chronic schizophrenia and 10 age-compatible individuals without psychiatric disorder. Eight hippocampal regions of interest and two internal control regions (primary motor and visual cortices) were identified on Nissl-stained sections. Morphometric measurements were made without knowledge of diagnosis by means of a computer-based image analysis system. The patients exhibited smaller neuron size in the hippocampal regions relative to the control regions, which was significant only for the subiculum, CA1, and layer II of the entorhinal cortex. Neuron size in the control regions was nearly identical in the two groups. No significant differences in neuron density or in variability of neuronal axis orientation were identified for any region. There was no correlation between neuron size in any area and several potentially confounding variables (age, post-mortem interval, neuroleptic exposure, sex, brain hemisphere studied, duration of illness), with the exception of a negative correlation with age in layer II of the entorhinal cortex. Regression analyses indicated that the findings could not be attributed to these age effects. The subiculum, entorhinal cortex, and CA1 are the major subfields of the hippocampal region that maintain the afferent and efferent connections of the hippocampus with widespread cortical and subcortical targets. The smaller size of neurons in these subfields may reflect the presence of structural or functional impairments that disrupt these connections, which in turn could have important behavioral sequelae.

  11. Dancing or Fitness Sport? The Effects of Two Training Programs on Hippocampal Plasticity and Balance Abilities in Healthy Seniors.

    Science.gov (United States)

    Rehfeld, Kathrin; Müller, Patrick; Aye, Norman; Schmicker, Marlen; Dordevic, Milos; Kaufmann, Jörn; Hökelmann, Anita; Müller, Notger G

    2017-01-01

    Age-related degenerations in brain structure are associated with balance disturbances and cognitive impairment. However, neuroplasticity is known to be preserved throughout lifespan and physical training studies with seniors could reveal volume increases in the hippocampus (HC), a region crucial for memory consolidation, learning and navigation in space, which were related to improvements in aerobic fitness. Moreover, a positive correlation between left HC volume and balance performance was observed. Dancing seems a promising intervention for both improving balance and brain structure in the elderly. It combines aerobic fitness, sensorimotor skills and cognitive demands while at the same time the risk of injuries is low. Hence, the present investigation compared the effects of an 18-month dancing intervention and traditional health fitness training on volumes of hippocampal subfields and balance abilities. Before and after intervention, balance was evaluated using the Sensory Organization Test and HC volumes were derived from magnetic resonance images (3T, MP-RAGE). Fourteen members of the dance (67.21 ± 3.78 years, seven females), and 12 members of the fitness group (68.67 ± 2.57 years, five females) completed the whole study. Both groups revealed hippocampal volume increases mainly in the left HC (CA1, CA2, subiculum). The dancers showed additional increases in the left dentate gyrus and the right subiculum. Moreover, only the dancers achieved a significant increase in the balance composite score. Hence, dancing constitutes a promising candidate in counteracting the age-related decline in physical and mental abilities.

  12. MR imaging findings of hypertrophic olivary degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-06-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions.

  13. Changes in ganglion cells during retinal degeneration.

    Science.gov (United States)

    Saha, Susmita; Greferath, Ursula; Vessey, Kirstan A; Grayden, David B; Burkitt, Anthony N; Fletcher, Erica L

    2016-08-04

    Inherited retinal degeneration such as retinitis pigmentosa (RP) is associated with photoreceptor loss and concomitant morphological and functional changes in the inner retina. It is not known whether these changes are associated with changes in the density and distribution of synaptic inputs to retinal ganglion cells (RGCs). We quantified changes in ganglion cell density in rd1 and age-matched C57BL/6J-(wildtype, WT) mice using the immunocytochemical marker, RBPMS. Our data revealed that following complete loss of photoreceptors, (∼3months of age), there was a reduction in ganglion cell density in the peripheral retina. We next examined changes in synaptic inputs to A type ganglion cells by performing double labeling experiments in mice with the ganglion cell reporter lines, rd1-Thy1 and age-matched wildtype-Thy1. Ribbon synapses were identified by co-labelling with CtBP2 (RIBEYE) and conventional synapses with the clustering molecule, gephyrin. ON RGCs showed a significant reduction in RIBEYE-immunoreactive synapse density while OFF RGCs showed a significant reduction in the gephyrin-immmunoreactive synapse density. Distribution patterns of both synaptic markers across the dendritic trees of RGCs were unchanged. The change in synaptic inputs to RGCs was associated with a reduction in the number of immunolabeled rod bipolar and ON cone bipolar cells. These results suggest that functional changes reported in ganglion cells during retinal degeneration could be attributed to loss of synaptic inputs. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Getting superstring amplitudes by degenerating Riemann surfaces

    International Nuclear Information System (INIS)

    Matone, Marco; Volpato, Roberto

    2010-01-01

    We explicitly show how the chiral superstring amplitudes can be obtained through factorisation of the higher genus chiral measure induced by suitable degenerations of Riemann surfaces. This powerful tool also allows to derive, at any genera, consistency relations involving the amplitudes and the measure. A key point concerns the choice of the local coordinate at the node on degenerate Riemann surfaces that greatly simplifies the computations. As a first application, starting from recent ansaetze for the chiral measure up to genus five, we compute the chiral two-point function for massless Neveu-Schwarz states at genus two, three and four. For genus higher than three, these computations include some new corrections to the conjectural formulae appeared so far in the literature. After GSO projection, the two-point function vanishes at genus two and three, as expected from space-time supersymmetry arguments, but not at genus four. This suggests that the ansatz for the superstring measure should be corrected for genus higher than four.

  15. MR imaging findings of hypertrophic olivary degeneration

    International Nuclear Information System (INIS)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik

    1997-01-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions

  16. Vitreous in lattice degeneration of retina.

    Science.gov (United States)

    Foos, R Y; Simons, K B

    1984-05-01

    A localized pocket of missing vitreous invariably overlies lattice degeneration of the retina. Subjects with lattice also have a higher rate of rhegmatogenous retinal detachment, which is usually a complication of retinal tears. The latter are in turn a result of alterations in the central vitreous--that is, synchysis senilis leading to posterior vitreous detachment. In order to determine if there is either an association or a deleterious interaction between the local and central lesions of the vitreous in eyes with lattice, a comparison was made in autopsy eyes with and without lattice the degree of synchysis and rate of vitreous detachment. Results show no association between the local and central vitreous lesions, indicating that a higher rate of vitreous detachment is not the basis for the higher rate of retinal detachment in eyes with lattice. Also, there was no suggestion of deleterious interaction between the local and central vitreous lesions, either through vitreodonesis as a basis for precocious vitreous detachment, or through a greater degree of synchysis as a basis for interconnection of local and central lacunae (which could extend the localized retinal detachment in eyes with holes in lattice degeneration).

  17. Visual signs and symptoms of corticobasal degeneration.

    Science.gov (United States)

    Armstrong, Richard A

    2016-11-01

    Corticobasal degeneration is a rare, progressive neurodegenerative disease and a member of the 'parkinsonian' group of disorders, which also includes Parkinson's disease, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. The most common initial symptom is limb clumsiness, usually affecting one side of the body, with or without accompanying rigidity or tremor. Subsequently, the disease affects gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Corticobasal degeneration can be difficult to distinguish from other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid clinical diagnosis. Typical ocular features include increased latency of saccadic eye movements ipsilateral to the side exhibiting apraxia, impaired smooth pursuit movements and visuo-spatial dysfunction, especially involving spatial rather than object-based tasks. Less typical features include reduction in saccadic velocity, vertical gaze palsy, visual hallucinations, sleep disturbance and an impaired electroretinogram. Aspects of primary vision such as visual acuity and colour vision are usually unaffected. Management of the condition to deal with problems of walking, movement, daily tasks and speech problems is an important aspect of the disease. © 2016 Optometry Australia.

  18. Metabolic anatomy of paraneoplastic cerebellar degeneration

    International Nuclear Information System (INIS)

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-01-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18 F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis

  19. Progranulin in frontotemporal lobar degeneration and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hutton Michael L

    2007-02-01

    Full Text Available Abstract Progranulin (PGRN is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD. Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs. While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.

  20. Metabolic anatomy of paraneoplastic cerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  1. Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid.

    Science.gov (United States)

    Nadler, J V; Perry, B W; Cotman, C W

    1980-01-20

    Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum and stratum oriens of area CA1. The responses of intact afferents to such lesions were then examined histologically. The hippocampal mossy fibers densely reinnervated the inner portion of the dentate molecular layer after bilateral destruction of CA4 neurons and to a lesser extent after unilateral destruction. Septohippocampal fibers replaced CA4-derived fibers in the dentate molecular layer only after particularly extensive bilateral CA4 lesions. Medial perforant path fibers showed no anatomical response to any of these lesions. Neither septohippocampal, temporoammonic nor mossy fibers proliferated in or grew into the denervated laminae of area CA1. These results show a preferential ordering in the reinnervation of dentate granule cells which is not readily explained by proximity to the degenerating fibers and also that removal of CA3-CA4-derived innervation more readily elicits translaminar growth in the fascia dentata than in area CA1. These results may be relevant to clinical situations in which neurons of the hippocampal end-blade are lost.

  2. Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

    Science.gov (United States)

    Khan, Archie A; Shekh-Ahmad, Tawfeeq; Khalil, Ayatakin; Walker, Matthew C; Ali, Afia B

    2018-03-25

    A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry. Electrophysiological intracellular whole-cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy (in vivo kainic acid-induced) and in vitro (Mg 2+ -free-induced) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg kg -1 ) at zero time and 90 minutes post status epilepticus (SE) induced with kainic acid. Bath-application of CBD (10 μM), dampened excitability at unitary synapses between pyramidal cells, but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK, and pyramidal cells in a cell type-specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction of atrophy and death of PV- and CCK-expressing interneurons after CBD treatment. In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function. This article is protected by copyright. All rights reserved.

  3. Spatial relational memory requires hippocampal adult neurogenesis.

    Directory of Open Access Journals (Sweden)

    David Dupret

    Full Text Available The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

  4. Gene-environment effects on hippocampal neurodevelopment

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    factors. Hence, a deeper understanding is needed of how cortical neurodevelopmental deficiencies can arise from such gene-environment interactions. The convergence of genetic and environmental risk factors is a recent field of research. It is now clear that disease, infection and stress factors may...... disrupt the normal function of neurodevelopmental genes. Here, the transcriptional repressor Zbtb20, which we and others have shown is a master regulator of hippocampal neurodevelopment, deserves special interest. We study the possibility that environmental factors such as steroid hormones, cytokines......Mental disorders like schizophrenia and autism put a heavy load on today’s societies, creating a steady call for revealing underlying disease mechanisms and the development of effective treatments. The etiology of major psychiatric illnesses is complex involving gene by environment susceptibility...

  5. Tau protein and adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Almudena eFuster-Matanzo

    2012-07-01

    Full Text Available Tau protein is a microtubule associated protein found in the axonal compartment that stabilizes neuronal microtubules under normal physiological conditions. Tau metabolism has attracted much attention because of its role in neurodegenerative disorders called tauopathies, mainly Alzheimer disease. Here, we review recent findings suggesting that axonal outgrowth in subgranular zone during adult hippocampal neurogenesis requires a dynamic microtubule network and tau protein facilitates to maintain that dynamic cytoskeleton. Those functions are carried out in part by tau isoform with only three microtubule-binding domains (without exon 10 and by presence of hypherphosphorylated tau forms. Thus, tau is a good marker and a valuable tool to study new axons in adult neurogenesis.

  6. Hummingbirds have a greatly enlarged hippocampal formation.

    Science.gov (United States)

    Ward, Brian J; Day, Lainy B; Wilkening, Steven R; Wylie, Douglas R; Saucier, Deborah M; Iwaniuk, Andrew N

    2012-08-23

    Both field and laboratory studies demonstrate that hummingbirds (Apodiformes, Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal information that hummingbirds must retain and use daily is probably subserved by the hippocampal formation (HF), and therefore, hummingbirds should have a greatly expanded HF. Here, we compare the relative size of the HF in several hummingbird species with that of other birds. Our analyses reveal that the HF in hummingbirds is significantly larger, relative to telencephalic volume, than any bird examined to date. When expressed as a percentage of telencephalic volume, the hummingbird HF is two to five times larger than that of caching and non-caching songbirds, seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies their ability to remember the location, distribution and nectar content of flowers, but more detailed analyses are required to determine the extent to which this arises from an expansion of HF or a decrease in size of other brain regions.

  7. Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

    Science.gov (United States)

    Geil, Chelsea R.; Hayes, Dayna M.; McClain, Justin A.; Liput, Daniel J.; Marshall, S. Alex; Chen, Kevin Y.; Nixon, Kimberly

    2014-01-01

    Adult neurogenesis is now widely accepted as an important contributor to hippocampal integrity and function but also dysfunction when adult neurogenesis is affected in neuropsychiatric diseases such as alcohol use disorders. Excessive alcohol consumption, the defining characteristic of alcohol use disorders, results in a variety of cognitive and behavioral impairments related wholly or in part to hippocampal structure and function. Recent preclinical work has shown that adult neurogenesis may be one route by which alcohol produces hippocampal neuropathology. Alcohol is a pharmacologically promiscuous drug capable of interfering with adult neurogenesis through multiple mechanisms. This review will discuss the primary mechanisms underlying alcohol-induced changes in adult hippocampal neurogenesis including alcohol's effects on neurotransmitters, CREB and its downstream effectors, and the neurogenic niche. PMID:24842804

  8. DEVELOPMENTAL HYPOTHYROIDISM IMPAIRS HIPPOCAMPAL LEARNING AND SYNAPTIC TRANSMISSION IN VIVO.

    Science.gov (United States)

    A number of environmental chemicals have been reported to alter thyroid hormone (TH) function. It is well established that severe hypothyroidism during critical periods of brain development leads to alterations in hippocampal structure and learning deficits, yet evaluation of ...

  9. Rhinal-hippocampal EEG coherence is reduced during human sleep.

    NARCIS (Netherlands)

    Fell, J.; Staedtgen, M.; Burr, W.; Kockelmann, E.; Helmstaedter, C.; Schaller, C.; Elger, C.E.; Fernandez, G.S.E.

    2003-01-01

    The deficiency of declarative memory compared with waking state is an often overlooked characteristic of sleep. Here, we investigated whether rhinal-hippocampal coherence, an electrophysiological correlate of declarative memory formation, is significantly altered during sleep as compared with waking

  10. The impact of sleep loss on hippocampal function

    OpenAIRE

    Prince, Toni-Moi; Abel, Ted

    2013-01-01

    Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-lear...

  11. Le Projet hippocampe devient un important protagoniste de la ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Projet hippocampe devient un important protagoniste de la conservation de la faune marine. 29 octobre 2012. Image. Stephen Dale. Des effets durables. Pour certains, le Projet hippocampe est un organisme qui a mobilisé des collectivités de pêcheurs pauvres des Philippines pour créer des dizaines d'aires protégées ...

  12. Automated hippocampal segmentation in patients with epilepsy: Available free online

    Science.gov (United States)

    Winston, Gavin P; Cardoso, M Jorge; Williams, Elaine J; Burdett, Jane L; Bartlett, Philippa A; Espak, Miklos; Behr, Charles; Duncan, John S; Ourselin, Sebastien

    2013-01-01

    Purpose Hippocampal sclerosis, a common cause of refractory focal epilepsy, requires hippocampal volumetry for accurate diagnosis and surgical planning. Manual segmentation is time-consuming and subject to interrater/intrarater variability. Automated algorithms perform poorly in patients with temporal lobe epilepsy. We validate and make freely available online a novel automated method. Methods Manual hippocampal segmentation was performed on 876, 3T MRI scans and 202, 1.5T scans. A template database of 400 high-quality manual segmentations was used to perform automated segmentation of all scans with a multi-atlas–based segmentation propagation method adapted to perform label fusion based on local similarity to ensure accurate segmentation regardless of pathology. Agreement between manual and automated segmentations was assessed by degree of overlap (Dice coefficient) and comparison of hippocampal volumes. Key Findings The automated segmentation algorithm provided robust delineation of the hippocampi on 3T scans with no more variability than that seen between different human raters (Dice coefficients: interrater 0.832, manual vs. automated 0.847). In addition, the algorithm provided excellent results with the 1.5T scans (Dice coefficient 0.827), and automated segmentation remained accurate even in small sclerotic hippocampi. There was a strong correlation between manual and automated hippocampal volumes (Pearson correlation coefficient 0.929 on the left and 0.941 on the right in 3T scans). Significance We demonstrate reliable identification of hippocampal atrophy in patients with hippocampal sclerosis, which is crucial for clinical management of epilepsy, particularly if surgical treatment is being contemplated. We provide a free online Web-based service to enable hippocampal volumetry to be available globally, with consequent greatly improved evaluation of those with epilepsy. PMID:24151901

  13. Sparse encoding of automatic visual association in hippocampal networks

    DEFF Research Database (Denmark)

    Hulme, Oliver J; Skov, Martin; Chadwick, Martin J

    2014-01-01

    by these stimuli. Using multivariate Bayesian decoding, we show that human hippocampal and temporal neocortical structures host sparse associative representations that are automatically triggered by visual input. Furthermore, as predicted theoretically, there was a significant increase in sparsity in the Cornu...... for the sparse encoding of associative density. In the absence of reportability or attentional confounds, this charts a distribution of visual associative representations within hippocampal populations and their temporal lobe afferent fields, and demonstrates the viability of retrospective associative sampling...

  14. FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

    Directory of Open Access Journals (Sweden)

    Cao Huang

    2011-03-01

    Full Text Available Fused in Sarcoma (FUS proteinopathy is a feature of frontotemporal lobar dementia (FTLD, and mutation of the fus gene segregates with FTLD and amyotrophic lateral sclerosis (ALS. To study the consequences of mutation in the fus gene, we created transgenic rats expressing the human fus gene with or without mutation. Overexpression of a mutant (R521C substitution, but not normal, human FUS induced progressive paralysis resembling ALS. Mutant FUS transgenic rats developed progressive paralysis secondary to degeneration of motor axons and displayed a substantial loss of neurons in the cortex and hippocampus. This neuronal loss was accompanied by ubiquitin aggregation and glial reaction. While transgenic rats that overexpressed the wild-type human FUS were asymptomatic at young ages, they showed a deficit in spatial learning and memory and a significant loss of cortical and hippocampal neurons at advanced ages. These results suggest that mutant FUS is more toxic to neurons than normal FUS and that increased expression of normal FUS is sufficient to induce neuron death. Our FUS transgenic rats reproduced some phenotypes of ALS and FTLD and will provide a useful model for mechanistic studies of FUS-related diseases.

  15. The effects of hormones and physical exercise on hippocampal structural plasticity.

    Science.gov (United States)

    Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

    2016-04-01

    The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Delivery systems for the treatment of degenerated intervertebral discs

    NARCIS (Netherlands)

    Blanquer, S. B. G.; Grijpma, D. W.; Poot, A. A.

    The intervertebral disc (ND) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production,

  17. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  18. Lattice degeneration of the retina and retinal detachment.

    Science.gov (United States)

    Semes, L P

    1992-01-01

    Lattice retinal degeneration is considered the most significant peripheral retinal disorder potentially predisposing to retinal breaks and retinal detachment. Lattice degeneration affects the vitreous and inner retinal layers with secondary changes as deep as the retinal pigment epithelium and perhaps the choriocapillaris. Variations in clinical appearance are the rule; geographically, lattice lesions favor the vertical meridians between the equator and the ora serrata. Lattice degeneration begins early in life and has been reported in sequential generations of the same family. Along with its customary bilateral occurrence, lattice shares other characteristics of a dystrophy. The association between the vitreous and retina in lattice lesions may be responsible for the majority of lattice-induced retinal detachments. The tumultuous event of posterior vitreous separation in the presence of abnormally strong vitreoretinal adherence is the trigger for a retinal tear that, in turn, may lead to retinal detachment. Although retinal holes in young patients with lattice degeneration may play a role in the evolution of retinal detachment, the clinical course of lattice degeneration seems to be one of dormancy rather than of progressive change. This discussion outlines the pathophysiology of lattice retinal degeneration and the relationship of pathophysiology to clinical presentation. The epidemiology of lattice degeneration is summarized, as are the possible precursors to retinal detachment. A clinical characterization of the natural history of lattice degeneration is offered, and interventions for complications are described. To conclude, management strategies from a primary-care standpoint are reviewed.

  19. Viscosity solution of linear regulator quadratic for degenerate diffusions

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The paper studied a linear regulator quadratic control problem for degenerate Hamilton-Jacobi-Bellman (HJB equation. We showed the existence of viscosity properties and established a unique viscosity solution of the degenerate HJB equation associated with this problem by the technique of viscosity solutions.

  20. Olodaterol Attenuates Citric Acid-Induced Cough in Naïve and Ovalbumin-Sensitized and Challenged Guinea Pigs

    Science.gov (United States)

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known. PMID:25781609

  1. Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells.

    Science.gov (United States)

    Lee, Kuan-Wei; Thiyagarajan, Varadharajan; Sie, Huei-Wun; Cheng, Ming-Fan; Tsai, May-Jywan; Chia, Yi-Chen; Weng, Ching-Feng

    2014-09-01

    Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate cells (HSCs), previously termed fat- or vitamin A-storing cells, can transdifferentiate into myofibroblast-like cells and are the most relevant cell type for overproduction of extracellular matrix (ECM) and development of liver fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs remains unclear. This study investigates the regulatory effect of natural compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have shown a significant effect on cell proliferation with oil red O staining and Western blot confirming that OA and PA induce fat storage ability and autophagy protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and benzyl cinnamate treatment have shown no effect on the autophagy protein expression. Nevertheless, cells pretreated with OA and PA then treated with rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway, the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment. However, there were no significant changes in PI3K-Class III and Beclin-1 protein expressions found to imply that this autophagy is unrelated to the mTOR-independent pathway. Taken together, the present study unveils rutin and curcumin as a possible effective stimulation for fatty acid-induced autophagy via mTOR-dependent pathways in NHSC. We further suggest the benefits of these natural compounds for alleviating liver fibrosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Activation of BK(Ca channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Guang Ma

    Full Text Available BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+-activated potassium (BK(Ca channel in zoledronic acid-induced apoptosis of estrogen receptor (ER-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293 cells which were transfected with functional BK(Ca α-subunit (hSloα. Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca channels, and then activation of BK(Ca channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+ and a concomitant depolarization of mitochondrial membrane potential (Δψm in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.

  3. Hippocampal correlates of depression in healthy elderly adults.

    Science.gov (United States)

    Ezzati, Ali; Zimmerman, Molly E; Katz, Mindy J; Lipton, Richard B

    2013-12-01

    Mixed findings have been reported on the relationship between hippocampal integrity and major depression in clinical populations. Few neuroimaging studies have investigated associations between hippocampal measures and depressive symptoms in nondemented older adults. Here, we address this issue by imaging 36 nondemented adults over age 70 from the Einstein Aging Study, a community-based sample from the Bronx, NY. Depressive symptoms were assessed using the 15-item Geriatric Depression scale (GDS). Clinically significant depression was defined using a cut-off score of 5 or greater. Hippocampal data included MRI-derived volume data normalized to midsagittal area and MRS-derived N-acetylaspartate to creatine ratios (NAA/Cr). Our result indicates that smaller total hippocampal volume was associated with higher GDS scores, but there were no significant association between hippocampal NAA/Cr and GDS score. These effects were consistent after controlling for age, education, and gender. Reduction in hippocampal volume could represent a risk factor or a consequence of depression in older adults. Further studies are needed to better understand the role of the hippocampus in the development and experience of depression in older adults. Copyright © 2013 Wiley Periodicals, Inc.

  4. Two reentrant pathways in the hippocampal-entorhinal system.

    Science.gov (United States)

    Kloosterman, Fabian; van Haeften, Theo; Lopes da Silva, Fernando H

    2004-01-01

    The entorhinal cortex has long been recognized as an important interface between the hippocampal formation and the neocortex. The notion of bidirectional connections between the entorhinal cortex and the hippocampal formation have led to the suggestion that hippocampal output originating in CA1 and subiculum may reenter hippocampal subfields via the entorhinal cortex. To investigate this, we used simultaneous multi-site field potential recordings and current source density analysis in the entorhinal cortex and hippocampal formation of the rat in vivo. Under ketamine/xylazine anesthesia, we found that repetitive stimulation of subiculum or Schaffer collaterals facilitated entorhinal responses, such that a population spike appeared in layer III. In addition, a current sink in stratum lacunosum-moleculare of area CA1 was found, that followed responses in the entorhinal cortex, indicating reentrance into this area. Responses indicating reentrance in the dentate gyrus were not found under ketamine/xylazine anesthesia, but were readily evoked under urethane anesthesia. Reentrance into CA1 was also encountered under urethane anesthesia. These results suggest that parallel, but possibly functionally distinct, connections are present between the output of the hippocampal formation and cells in layers III and II of the entorhinal cortex that project to area CA1 and the dentate gyrus, respectively. 2004 Wiley-Liss, Inc.

  5. Frequency metrology in quantum degenerate helium

    Directory of Open Access Journals (Sweden)

    Vassen Wim

    2013-08-01

    Full Text Available We have measured the absolute frequency of the 1557-nm doubly forbidden transition between the two metastable states of helium, 2 3S1 (lifetime 8000 s and 2 1S0 (lifetime 20 ms, with 1 kHz precision. With an Einstein coefficient of 10−7 s−1 this is one of weakest optical transitions ever measured. The measurement was performed in a Bose-Einstein condensate of 4He* as well as in a Degenerate Fermi Gas of 3He*, trapped in a crossed dipole trap. From the isotope shift we deduced the nuclear charge radius difference between the α-particle and the helion. Our value differs by 4σ with a very recent result obtained on the 2 3S → 2 3P transition.

  6. Nearly degenerate neutrinos, Supersymmetry and radiative corrections

    CERN Document Server

    Casas, J A; Ibarra, Alejandro; Navarro, I

    2000-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate with a mass matrix of the bimaximal mixing type. We study this scenario in the MSSM framework, finding that if neutrino masses are produced by a see-saw mechanism, the radiative corrections give rise to mass splittings and mixing angles that can accommodate the atmospheric and the (large angle MSW) solar neutrino oscillations. This provides a natural origin for the $\\Delta m^2_{sol} << \\Delta m^2_{atm}$ hierarchy. On the other hand, the vacuum oscillation solution to the solar neutrino problem is always excluded. We discuss also in the SUSY scenario other possible effects of radiative corrections involving the new neutrino Yukawa couplings, including implications for triviality limits on the Majorana mass, the infrared fixed point value of the top Yukawa coupling, and gauge coupling and bottom-tau unification.

  7. Prevention of Age-Related Macular Degeneration.

    Science.gov (United States)

    Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv

    2017-01-01

    Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  8. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    Science.gov (United States)

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  9. Degenerate R-S perturbation theory

    Science.gov (United States)

    Hirschfelder, J. O.; Certain, P. R.

    1973-01-01

    A concise, systematic procedure is given for determining the Rayleigh-Schrodinger energies and wave functions of degenerate states to arbitrarily high orders even when the degeneracies of the various states are resolved in arbitrary orders. The procedure is expressed in terms of an iterative cycle in which the energy through the (2n+1)st order is expressed in terms of the partially determined wave function through the n-th order. Both a direct and an operator derivation are given. The two approaches are equivalent and can be transcribed into each other. The direct approach deals with the wave functions (without the use of formal operators) and has the advantage that it resembles the usual treatment of nondegenerate perturbations and maintains close contact with the basic physics. In the operator approach, the wave functions are expressed in terms of infinite order operators which are determined by the successive resolution of the space of the zeroth order functions.

  10. Conjunctival intraepithelial neoplasia with corneal furrow degeneration

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2014-01-01

    Full Text Available A 68-year-old man presented with redness of left eye since six months. Examination revealed bilateral corneal furrow degeneration. Left eye lesion was suggestive of conjunctival squamous cell carcinoma, encroaching on to cornea. Anterior segment optical coherence tomography (AS-OCT confirmed peripheral corneal thinning. Fluorescein angiography confirmed intrinsic vascularity of lesion. Patient was managed with "no touch" surgical excision, dry keratectomy without alcohol, cryotherapy, and primary closure. Pathologic examination of removed tissue confirmed clinical diagnosis. Management of this particular case required modification of standard treatment protocol. Unlike the alcohol-assisted technique of tumor dissection described, ethyl alcohol was not used for risk of corneal perforation due to underlying peripheral corneal thinning. Likewise, topical steroids were withheld in the post-operative period. Three weeks post-operatively, left eye was healing well. Hence, per-operative usage of absolute alcohol and post-operative use of topical steroids may be best avoided in such eyes.

  11. Formation of Degenerate Band Gaps in Layered Systems

    Directory of Open Access Journals (Sweden)

    Alexey P. Vinogradov

    2012-06-01

    Full Text Available In the review, peculiarities of spectra of one-dimensional photonic crystals made of anisotropic and/or magnetooptic materials are considered. The attention is focused on band gaps of a special type—the so called degenerate band gaps which are degenerate with respect to polarization. Mechanisms of formation and properties of these band gaps are analyzed. Peculiarities of spectra of photonic crystals that arise due to the linkage between band gaps are discussed. Particularly, it is shown that formation of a frozen mode is caused by linkage between Brillouin and degenerate band gaps. Also, existence of the optical Borrmann effect at the boundaries of degenerate band gaps and optical Tamm states at the frequencies of degenerate band gaps are analyzed.

  12. Computer assisted characterization of cervical intervertebral disc degeneration in MRI

    Science.gov (United States)

    Michopoulou, S.; Boniatis, I.; Costaridou, L.; Cavouras, D.; Panagiotopoulos, E.; Panayiotakis, G.

    2009-05-01

    A texture-based pattern recognition system is proposed for the automatic characterization of cervical intervertebral disc degeneration from saggital magnetic resonance images of the spine. A case sample of 50 manually segmented ROIs, corresponding to 25 normal and 25 degenerated discs, was analyzed and textural features were generated from each disc-ROI. Student's t-test verified the existence of statistically significant differences between textural feature values generated from normal and degenerated discs. This finding is indicative of disc image texture differentiation due to the degeneration of the disc. The generated features were employed in the design of a pattern recognition system based on the Least Squares Minimum Distance classifier. The system achieved a classification accuracy of 94{%} and it may be of value to physicians for the assessment of cervical intervertebral disc degeneration in MRI.

  13. [Lattice degeneration of the peripheral retina: ultrastructural study].

    Science.gov (United States)

    Bec, P; Malecaze, F; Arne, J L; Mathis, A

    1985-01-01

    The ultrastructural study of a case of snail track degeneration shows the presence of lipid inclusions in both the glial and the macrophage cells in every layer of the retina, and the existence of intraretinal fibers different from collagen fibers appearing to be glial filaments similar to those found in astrocytic gliomes and to the Rosenthal fibers observed in senile nervous cells. Other features were thinning of the retina and absence of blood vessels in the retina. There are no abnormalities of the vitreo-retinal juncture. All the lesions are in agreement with those observed by Daicker [Ophthalmologica, Basel 165: 360-365, 1972; Klin. Mbl. Augenheilk. 172: 581-583, 1978] with some differences, however. They are different from those found in lattice degeneration. They show that snail track degeneration is a specific form of peripheral retinal degeneration which is quite different from lattice degeneration and must not be considered similar.

  14. The effect of kyphoscoliosis on intervertebral disc degeneration in dogs.

    Science.gov (United States)

    Faller, Kiterie; Penderis, Jacques; Stalin, Catherine; Guevar, Julien; Yeamans, Carmen; Gutierrez-Quintana, Rodrigo

    2014-06-01

    In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann's grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in older dogs, all IVDs - including the non-adjacents - showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

    2001-01-01

    The excitotoxic profiles of (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), (RS)-2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) were evaluated using cellular uptake of propidium iodide (PI) as a measure......) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed...... by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

  16. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  17. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  18. Role of adult hippocampal neurogenesis in stress resilience

    Directory of Open Access Journals (Sweden)

    Brunno R. Levone

    2015-01-01

    Full Text Available There is a growing appreciation that adult hippocampal neurogenesis plays a role in emotional and cognitive processes related to psychiatric disorders. Although many studies have investigated the effects of stress on adult hippocampal neurogenesis, most have not focused on whether stress-induced changes in neurogenesis occur specifically in animals that are more resilient or more susceptible to the behavioural and neuroendocrine effects of stress. Thus, in the present review we explore whether there is a clear relationship between stress-induced changes in adult hippocampal neurogenesis, stress resilience and antidepressant-induced recovery from stress-induced changes in behaviour. Exposure to different stressors is known to reduce adult hippocampal neurogenesis, but some stressors have also been shown to exert opposite effects. Ablation of neurogenesis does not lead to a depressive phenotype, but it can enhance responsiveness to stress and affect stress susceptibility. Monoaminergic-targeted antidepressants, environmental enrichment and adrenalectomy are beneficial for reversing stress-induced changes in behaviour and have been shown to do so in a neurogenesis-dependant manner. In addition, stress and antidepressants can affect hippocampal neurogenesis, preferentially in the ventral hippocampus. Together, these data show that adult hippocampal neurogenesis may play a role in the neuroendocrine and behavioural responses to stress, although it is not yet fully clear under which circumstances neurogenesis promotes resilience or susceptibility to stress. It will be important that future studies carefully examine how adult hippocampal neurogenesis can contribute to stress resilience/susceptibility so that it may be appropriately exploited for the development of new and more effective treatments for stress-related psychiatric disorders.

  19. Hippocampal Hyperactivation in Presymptomatic Familial Alzheimer’s Disease

    Science.gov (United States)

    Quiroz, Yakeel T.; Budson, Andrew E.; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E.

    2011-01-01

    Objective The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer’s disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Methods Twenty carriers of the Alzheimer’s-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Philips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Results Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Interpretation Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD. PMID:21194156

  20. Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

    Science.gov (United States)

    Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

    2016-09-01

    In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD

  1. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  2. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  3. Effect of Opioid on Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-01-01

    Full Text Available During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs’ effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal’s opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse.

  4. D-serine increases adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Sebastien eSultan

    2013-08-01

    Full Text Available Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. The neurogenic niche regulates the stem cell proliferation and the differentiation and survival of new neurons and a major contributor to the neurogenic niche are astrocytes. Among the molecules secreted by astrocytes, D-serine is an important gliotransmitter and is a co-agonist of the glutamate, N-methyl-D-aspartate (NMDA receptor. D-serine has been shown to enhance the proliferation of neural stem cells in vitro, but its effect on adult neurogenesis in vivo is unknown. Here, we tested the effect of exogenous administration of D-serine on adult neurogenesis in the mouse dentate gyrus. We found that 1 week of treatment with D-serine increased cell proliferation in vivo and in vitro and increased the density of neural stem cells and transit amplifying progenitors. Furthermore, D-serine increased the survival of newborn neurons. Together, these results indicate that D-serine treatment resulted in the improvement of several steps of adult neurogenesis in vivo.

  5. Trafficking of astrocytic vesicles in hippocampal slices

    International Nuclear Information System (INIS)

    Potokar, Maja; Kreft, Marko; Lee, So-Young; Takano, Hajime; Haydon, Philip G.; Zorec, Robert

    2009-01-01

    The increasingly appreciated role of astrocytes in neurophysiology dictates a thorough understanding of the mechanisms underlying the communication between astrocytes and neurons. In particular, the uptake and release of signaling substances into/from astrocytes is considered as crucial. The release of different gliotransmitters involves regulated exocytosis, consisting of the fusion between the vesicle and the plasma membranes. After fusion with the plasma membrane vesicles may be retrieved into the cytoplasm and may continue to recycle. To study the mobility implicated in the retrieval of secretory vesicles, these structures have been previously efficiently and specifically labeled in cultured astrocytes, by exposing live cells to primary and secondary antibodies. Since the vesicle labeling and the vesicle mobility properties may be an artifact of cell culture conditions, we here asked whether the retrieving exocytotic vesicles can be labeled in brain tissue slices and whether their mobility differs to that observed in cell cultures. We labeled astrocytic vesicles and recorded their mobility with two-photon microscopy in hippocampal slices from transgenic mice with fluorescently tagged astrocytes (GFP mice) and in wild-type mice with astrocytes labeled by Fluo4 fluorescence indicator. Glutamatergic vesicles and peptidergic granules were labeled by the anti-vesicular glutamate transporter 1 (vGlut1) and anti-atrial natriuretic peptide (ANP) antibodies, respectively. We report that the vesicle mobility parameters (velocity, maximal displacement and track length) recorded in astrocytes from tissue slices are similar to those reported previously in cultured astrocytes.

  6. Acquired Nonpigmented Vitreous Cyst Associated With Lattice Degeneration.

    Science.gov (United States)

    Lu, Jing; Mai, Guiying; Liu, Ruyuan; Luo, Yan; Lu, Lin

    2017-10-01

    A 63-year-old male presented with a round-shaped floater and visual obscuration in the right eye. Clinical evaluation showed a nonpigmented vitreous cyst connected to a lattice degeneration by a stalk. Immunostaining of the vitreous cyst obtained from vitrectomy showed its origin of retinal neuroepithelium. The cyst was formed by continuous vitreous traction, which might tear up the disrupted retina at the area of lattice degeneration. This report added the lattice degeneration to the list of causes for the acquired vitreous cyst. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:856-858.]. Copyright 2017, SLACK Incorporated.

  7. [Clinical features and prognosis of retinal lattice degeneration].

    Science.gov (United States)

    Guo, X R

    1990-07-01

    110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand.

  8. Animal models of disc degeneration and major genetic strategies.

    Science.gov (United States)

    Sun, Fu; Qu, Ji-Ning; Zhang, Yin-Gang

    2013-01-01

    The establishment of a reliable animal model of lumbar disc degeneration (AMDD) is important for studying pathogenesis and evaluating treatment effectiveness. However, an ideal AMDD for use in laboratory studies has not yet been produced. This retrospective study reviews and compares several common AMDD and discusses their strengths and weaknesses. We also suggest a new method for establishing future AMDD. The identified genes associated with disc degeneration are susceptibility genes, which elevate risk but do not necessarily lead to disease occurrence. We propose to identify families with hereditary disc degeneration, find major casual genes with exome sequencing, and establish transgenic animal models. This approach may help us to build an improved AMDD.

  9. Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory.

    Science.gov (United States)

    Takada, S H; dos Santos Haemmerle, C A; Motta-Teixeira, L C; Machado-Nils, A V; Lee, V Y; Takase, L F; Cruz-Rizzolo, R J; Kihara, A H; Xavier, G F; Watanabe, I-S; Nogueira, M I

    2015-01-22

    Neonatal anoxia in rodents has been used to understand brain changes and cognitive dysfunction following asphyxia. This study investigated the time-course of cellular and subcellular changes and hippocampal cell death in a non-invasive model of anoxia in neonatal rats, using Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) to reveal DNA fragmentation, Fluoro-Jade® B (FJB) to show degenerating neurons, cleaved caspase-3 immunohistochemistry (IHC) to detect cells undergoing apoptosis, and transmission electron microscopy (TEM) to reveal fine ultrastructural changes related to cell death. Anoxia was induced by exposing postnatal day 1 (P1) pups to a flow of 100% gaseous nitrogen for 25 min in a chamber maintained at 37 °C. Control rats were similarly exposed to this chamber but with air flow instead of nitrogen. Brain changes following anoxia were evaluated at postnatal days 2, 14, 21 and 60 (P2, P14, P21 and P60). In addition, spatial reference memory following anoxia and control treatments was evaluated in the Morris water maze, starting at P60. Compared to their respective controls, P2 anoxic rats exhibited (1) higher TUNEL labeling in cornus ammonis (CA) 1 and the dentate gyrus (DG), (2) higher FJB-positive cells in the CA2-3, and (3) somato-dendritic swelling, mitochondrial injury and chromatin condensation in irregular bodies, as well as other subcellular features indicating apoptosis, necrosis, autophagy and excitotoxicity in the CA1, CA2-3 and DG, as revealed by TEM. At P14, P21 and P60, both groups showed small numbers of TUNEL-positive and FJB-positive cells. Stereological analysis at P2, P14, P21 and P60 revealed a lack of significant differences in cleaved caspase-3 IHC between anoxic and control subjects. These results suggest that the type of hippocampal cell death following neonatal anoxia is likely independent of caspase-3 activation. Neonatal anoxia induced deficits in acquisition and performance of spatial reference

  10. A Nonlinear Model for Hippocampal Cognitive Prosthesis: Memory Facilitation by Hippocampal Ensemble Stimulation

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Chan, Rosa H.M.; Sweatt, Andrew J.; Riley, Mitchell R.; Gerhardt, Gregory A.; Shin, Dae C.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Samuel A.

    2012-01-01

    Collaborative investigations have characterized how multineuron hippocampal ensembles encode memory necessary for subsequent successful performance by rodents in a delayed nonmatch to sample (DNMS) task and utilized that information to provide the basis for a memory prosthesis to enhance performance. By employing a unique nonlinear dynamic multi-input/multi-output (MIMO) model, developed and adapted to hippocampal neural ensemble firing patterns derived from simultaneous recorded CA1 and CA3 activity, it was possible to extract information encoded in the sample phase necessary for successful performance in the nonmatch phase of the task. The extension of this MIMO model to online delivery of electrical stimulation delivered to the same recording loci that mimicked successful CA1 firing patterns, provided the means to increase levels of performance on a trial-by-trial basis. Inclusion of several control procedures provides evidence for the specificity of effective MIMO model generated patterns of electrical stimulation. Increased utility of the MIMO model as a prosthesis device was exhibited by the demonstration of cumulative increases in DNMS task performance with repeated MIMO stimulation over many sessions on both stimulation and nonstimulation trials, suggesting overall system modification with continued exposure. Results reported here are compatible with and extend prior demonstrations and further support the candidacy of the MIMO model as an effective cortical prosthesis. PMID:22438334

  11. Cortico-hippocampal interaction and adaptive stimulus representation: A neurocomputational theory of associative learning and memory.

    NARCIS (Netherlands)

    Gluck, M.A.; Myers, C.E; Meeter, M.

    2005-01-01

    Computational models of the hippocampal region link psychological theories of associative learning with their underlying physiological and anatomical substrates. Our approach to theory development began with a broad description of the computations that depend on the hippocampal region in classical

  12. Qualitative and Quantitative Hippocampal MRI Assessments in Intractable Epilepsy

    Directory of Open Access Journals (Sweden)

    Paramdeep Singh

    2013-01-01

    Full Text Available Aims. To acquire normative data of hippocampal volumes and T2 relaxation times, to evaluate and compare qualitative and quantitative assessments in evaluating hippocampi in patients with different durations of intractable epilepsy, and to propose an imaging protocol based on performance of these techniques. Methods. MRI analysis was done in 50 nonepileptic controls and 30 patients with intractable epilepsy on 1.5T scanner. Visual assessment and hippocampal volumetry were done on oblique coronal IR/T2W and T1W MP-RAGE images, respectively. T2 relaxation times were measured using 16-echo Carr-Purcell-Meiboom-Gill sequence. Volumetric data was normalized for variation in head size between individuals. Patients were divided into temporal ( and extratemporal ( groups based on clinical and EEG localization. Results. In controls, right hippocampal volume was slightly more than the left with no effect of age or gender. In TLE patients, hippocampal volumetry provided maximum concordance with EEG. Visual assessment of unilateral pathology concurred well with measured quantitative values but poorly in cases with bilateral pathologies. There were no significant differences of mean values between extratemporal group and controls group. Quantitative techniques detected mild abnormalities, undetected on visual assessment. Conclusions. Quantitative techniques are more sensitive to diagnose bilateral and mild unilateral hippocampal abnormalities.

  13. Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

    2011-01-01

    Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437

  14. Vitamin D and hippocampal development-the story so far.

    Science.gov (United States)

    Lardner, Anne L

    2015-01-01

    Epidemiological studies suggest that vitamin D insufficiency may be prevalent in young as well as older populations. The pleiotropic effects of vitamin D are now beyond dispute and a growing number of studies provide accumulating evidence of a role for vitamin D in brain development and function. A number of studies to date have investigated the effects of early-life vitamin D deprivation on adult hippocampus in animals and humans, and there is a growing body of evidence to suggest a role for this hormone in the development of selected hippocampal functions such as latent inhibition and hole board habituation in rats. There are few studies to date of vitamin D deprivation or supplementation on early hippocampal development in vivo. However, a small number of studies, mostly in vitro, point to a role for vitamin D in differentiation and development of hippocampal neurons. There is also limited evidence that supplementation with vitamin D following a period of deprivation is capable of restoring cellular activity and later function. Further avenues of future research are outlined including animal studies on the effects of vitamin D deprivation and inadequacy on early hippocampal biochemistry and function, e.g., measurement of BDNF levels, GABAergic activity, long-term potentiation (LTP) and spatial navigation. It also remains to be established if there are critical developmental windows during which vitamin D is required. In light of the importance of the hippocampus in LTP and spatial learning, further investigations on the early effects of vitamin D deprivation on hippocampal development are warranted.

  15. Remote semantic memory is impoverished in hippocampal amnesia.

    Science.gov (United States)

    Klooster, Nathaniel B; Duff, Melissa C

    2015-12-01

    The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Amyloid Beta Peptide Slows Down Sensory-Induced Hippocampal Oscillations

    Directory of Open Access Journals (Sweden)

    Fernando Peña-Ortega

    2012-01-01

    Full Text Available Alzheimer’s disease (AD progresses with a deterioration of hippocampal function that is likely induced by amyloid beta (Aβ oligomers. Hippocampal function is strongly dependent on theta rhythm, and disruptions in this rhythm have been related to the reduction of cognitive performance in AD. Accordingly, both AD patients and AD-transgenic mice show an increase in theta rhythm at rest but a reduction in cognitive-induced theta rhythm. We have previously found that monomers of the short sequence of Aβ (peptide 25–35 reduce sensory-induced theta oscillations. However, considering on the one hand that different Aβ sequences differentially affect hippocampal oscillations and on the other hand that Aβ oligomers seem to be responsible for the cognitive decline observed in AD, here we aimed to explore the effect of Aβ oligomers on sensory-induced theta rhythm. Our results show that intracisternal injection of Aβ1–42 oligomers, which has no significant effect on spontaneous hippocampal activity, disrupts the induction of theta rhythm upon sensory stimulation. Instead of increasing the power in the theta band, the hippocampus of Aβ-treated animals responds to sensory stimulation (tail pinch with an increase in lower frequencies. These findings demonstrate that Aβ alters induced theta rhythm, providing an in vivo model to test for therapeutic approaches to overcome Aβ-induced hippocampal and cognitive dysfunctions.

  17. Hippocampal-neocortical functional reorganization underlies children's cognitive development.

    Science.gov (United States)

    Qin, Shaozheng; Cho, Soohyun; Chen, Tianwen; Rosenberg-Lee, Miriam; Geary, David C; Menon, Vinod

    2014-09-01

    The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development-the transition from procedure-based to memory-based problem-solving strategies-are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal functional magnetic resonance imaging (fMRI) in 7-9-year-old children revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Longitudinal improvements in retrieval-strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval-strategy use continued to improve through adolescence into adulthood and was associated with decreased activation but more stable interproblem representations in the hippocampus. Our findings provide insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development.

  18. Hippocampal functional connectivity and episodic memory in early childhood.

    Science.gov (United States)

    Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L; Redcay, Elizabeth

    2016-06-01

    Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Altered Hippocampal Morphology in Unmedicated Patients with Major Depressive Illness

    Directory of Open Access Journals (Sweden)

    Carrie E Bearden

    2009-10-01

    Full Text Available Despite converging evidence that major depressive illness is associated with both memory impairment and hippocampal pathology, findings vary widely across studies and it is not known whether these changes are regionally specific. In the present study we acquired brain MRIs (magnetic resonance images from 31 unmedicated patients with MDD (major depressive disorder; mean age 39.2±11.9 years; 77% female and 31 demographically comparable controls. Three-dimensional parametric mesh models were created to examine localized alterations of hippocampal morphology. Although global volumes did not differ between groups, statistical mapping results revealed that in MDD patients, more severe depressive symptoms were associated with greater left hippocampal atrophy, particularly in CA1 (cornu ammonis 1 subfields and the subiculum. However, previous treatment with atypical antipsychotics was associated with a trend towards larger left hippocampal volume. Our findings suggest effects of illness severity on hippocampal size, as well as a possible effect of past history of atypical antipsychotic treatment, which may reflect prolonged neuroprotective effects. This possibility awaits confirmation in longitudinal studies.

  20. Hippocampal and amygdalar volumes in dissociative identity disorder.

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J; Bremner, J Douglas

    2006-04-01

    Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

  1. On degenerate metrics, dark matter and unification

    Science.gov (United States)

    Searight, Trevor P.

    2017-12-01

    A five-dimensional theory of relativity is presented which suggests that gravitation and electromagnetism may be unified using a degenerate metric. There are four fields (in the four-dimensional sense): a tensor field, two vector fields, and a scalar field, and they are unified with a combination of a gauge-like invariance and a reflection symmetry which means that both vector fields are photons. The gauge-like invariance implies that the fifth dimension is not directly observable; it also implies that charge is a constant of motion. The scalar field is analogous to the Brans-Dicke scalar field, and the theory tends towards the Einstein-Maxwell theory in the limit as the coupling constant tends to infinity. As there is some scope for fields to vary in the fifth dimension, it is possible for the photons to have wave behaviour in the fifth dimension. The wave behaviour has two effects: it gives mass to the photons, and it prevents them from interacting directly with normal matter. These massive photons still act as a source of gravity, however, and therefore they are candidates for dark matter.

  2. CERKL knockdown causes retinal degeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Marina Riera

    Full Text Available The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.

  3. Nerve degeneration in inguinal hernia specimens.

    Science.gov (United States)

    Amato, G; Ober, E; Romano, G; Salamone, G; Agrusa, A; Gulotta, G; Bussani, R

    2011-02-01

    The histological study of the herniated inguinal area is rare in the literature. This report is focused on the detection of structural changes of the nerves within tissues bordering the inguinal hernia of cadavers. Their physiopathological consequences are hypothesized. Primary inguinal hernia was diagnosed in 30 fresh cadavers. Tissue specimens from the inguinal region close to and around the hernia opening were excised for histological examination. A control of the data was achieved through tissue samples excised from equivalent sites of the inguinal region in 15 cadavers without hernia. The detected nerves in the inguinal area demonstrated pathological changes such as fibrotic degeneration, atrophy, and fatty dystrophy of the axons. The thickening of the perineural sheath was constantly seen. These findings were consistently present, independent of the hernia type. The detected nerve alterations lead us to imagine a worsening, or even the cessation, of the nervous impulse to the muscles, leading to atrophy and weakening of the abdominal wall. This could represent one of the multifactorial causes of hernia genesis.

  4. Correlations in a partially degenerate electron plasma

    Energy Technology Data Exchange (ETDEWEB)

    Chihara, Junzo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    The density-functional theory proves that an ion-electron mixture can be treated as a one-component liquid interacting only via a pairwise interaction in the evaluation of the ion-ion radial distribution function (RDF), and provides a set of integral equations: one is an integral equation for the ion-ion RDF and another for an effective ion-ion interaction, which depends on the ion-ion RDF. This formulation gives a set of integral equation to calculate plasma structures with combined use of the electron-electron correlations in a partially degenerate electron plasma. Therefore, it is important for this purpose to determine the electron-electron correlations at a arbitrary temperature. Here, they are calculated by the quantal version of the hypernetted chain (HNC) equation. On the basis of the jellium-vacancy model, the ionic and electronic structures of rubidium are calculated for the range from liquid metal to plasma states by increasing the temperature at the fixed density using the electron-correlation results. (author)

  5. Linear stochastic degenerate Sobolev equations and applications†

    Science.gov (United States)

    Liaskos, Konstantinos B.; Pantelous, Athanasios A.; Stratis, Ioannis G.

    2015-12-01

    In this paper, a general class of linear stochastic degenerate Sobolev equations with additive noise is considered. This class of systems is the infinite-dimensional analogue of linear descriptor systems in finite dimensions. Under appropriate assumptions, the mild and strong well-posedness for the initial value problem are studied using elements of the semigroup theory and properties of the stochastic convolution. The final value problem is also examined and it is proved that this is uniquely strongly solvable and the solution is continuously dependent on the final data. Based on the results of the forward and backward problem, the conditions for the exact controllability are investigated for a special but important class of these equations. The abstract results are illustrated by applications in complex media electromagnetics, in the one-dimensional stochastic Dirac equation in the non-relativistic limit and in a potential application in input-output analysis in economics. Dedicated to Professor Grigoris Kalogeropoulos on the occasion of his seventieth birthday.

  6. Radiotherapy in age-related macula degeneration

    International Nuclear Information System (INIS)

    Gripp, Stephan; Stammen, Johannes; Petersen, Claudia; Hartmann, Axel; Willers, Reinhart; Althaus, Christoph

    2002-01-01

    Purpose: To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study. Methods and Materials: From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation. Results: Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49-92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p=0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p=0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p<0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p=0.17) nor gender (p=0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints. Conclusion: Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients

  7. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  8. Magnonic triply-degenerate nodal points

    Science.gov (United States)

    Owerre, S. A.

    2017-12-01

    We generalize the concept of triply-degenerate nodal points to non-collinear antiferromagnets. Here, we introduce this concept to insulating quantum antiferromagnets on the decorated honeycomb lattice, with spin-1 bosonic quasiparticle excitations known as magnons. We demonstrate the existence of magnonic surface states with constant energy contours that form pairs of magnonic arcs connecting the surface projection of the magnonic triple nodal points. The quasiparticle excitations near the triple nodal points represent three-component bosons beyond that of magnonic Dirac, Weyl, and nodal-line cases. They can be regarded as a direct reflection of the intrinsic spin carried by magnons. Furthermore, we show that the magnonic triple nodal points can split into magnonic Weyl points, as the system transits from a non-collinear spin structure to a non-coplanar one with a non-zero scalar spin chirality. Our results not only apply to insulating antiferromagnets, but also provide a platform to seek for triple nodal points in metallic antiferromagnets.

  9. Symmetric corticobasal degeneration (S-CBD).

    Science.gov (United States)

    Hassan, Anhar; Whitwell, Jennifer L; Boeve, Bradley F; Jack, Clifford R; Parisi, Joseph E; Dickson, Dennis W; Josephs, Keith A

    2010-03-01

    Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, pCBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  10. An imbedding theorem and its applications in degenerate elliptic equations

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1988-06-01

    We improve the Rellich-Kondrachov theorem and apply it to study strongly degenerate and singular elliptic equations. We obtain the maximum principle, Harnacks's inequality and global regularity for solutions of those equations. (author). 11 refs

  11. The degenerate-internal-states approximation for cold collisions

    NARCIS (Netherlands)

    Maan, A.C.; Tiesinga, E.; Stoof, H.T.C.; Verhaar, B.J.

    1990-01-01

    The Degenerate-Internal-States approximation as well as its first-order correction are shown to provide a convenient method for calculating elastic and inelastic collision amplitudes for low temperature atomic scattering.

  12. Melange a Six Ondes Degenere dans les Absorbants Saturables

    Science.gov (United States)

    Blouin, Alain

    Issus d'une generalisation du melange a quatre ondes degenere, les melanges a n ondes degeneres sont utiles pour la mesure des divers ordres de la susceptibilite nonlineaire. Nous avons procede a l'etude theorique et experimentale du melange a six ondes degenere dans des absorbants isotropes et anisotropes. Pour l'analyse theorique, nous avons developpe une methode de calcul basee sur une approche holographique. Cette methode fut utilisee pour l'etude du melange a six ondes en regimes stationnaire et transitoire sous des conditions de faibles et de fortes saturations. Des experiences realisees a l'aide d'impulsions excitatrices de courte duree, soit 33 picosecondes, dans des verres dopes aux semi-conducteurs et dans la Rhodamine 6G en solution ont permis de verifier la validite de notre modele theorique. Nous avons aussi etudie les oscillateurs auto-pompes par melange a six ondes degenere.

  13. Determination of source terms in a degenerate parabolic equation

    International Nuclear Information System (INIS)

    Cannarsa, P; Tort, J; Yamamoto, M

    2010-01-01

    In this paper, we prove Lipschitz stability results for inverse source problems relative to parabolic equations. We use the method introduced by Imanuvilov and Yamamoto in 1998 based on Carleman estimates. What is new here is that we study a class of one-dimensional degenerate parabolic equations. In our model, the diffusion coefficient vanishes at one extreme point of the domain. Instead of the classical Carleman estimates obtained by Fursikov and Imanuvilov for non degenerate equations, we use and extend some recent Carleman estimates for degenerate equations obtained by Cannarsa, Martinez and Vancostenoble. Finally, we obtain Lipschitz stability results in inverse source problems for our class of degenerate parabolic equations both in the case of a boundary observation and in the case of a locally distributed observation

  14. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment.

    Science.gov (United States)

    Mathew, David J; Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V

    2016-07-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were also areas of white without pressure, chorioretinal scarring and retinal breaks. All the changes were limited to beyond the equator but were found to span 360 degrees. She was treated with barrage laser all around to prevent extension of the retinal detachment posteriorly. She remained stable till her latest follow-up two years after the barrage laser. This case is reported for its rarity with a discussion of the probable differential diagnoses. To the best of our knowledge, this is the first report of such findings in lattice degeneration.

  15. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally...... late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume....

  16. Citric acid induced promoted dispersion of Pt on the support and enhanced catalytic activities for a Pt-based catalyst

    Science.gov (United States)

    Cheng, Tianqiong; Wang, Jianli; Wang, Suning; Cui, Yajuan; Zhang, Hailong; Yan, Shuang; Yuan, Shandong; Chen, Yaoqiang

    2017-12-01

    Citric acid (CA), as the chelating agent, was introduced to obtain the enhanced Pt dispersion and catalytic activities for the Pt-based catalysts supported on oxygen-storage material. The role and content of CA were investigated systematically. It was found that the citric acid-assisted catalysts showed better Pt dispersion and smaller nanoparticle size of Pt. Thus, the catalyst had lower reduction temperature, preferable thermostability and possessed more oxidation state of Pt species under the oxidation atmosphere. The citric acid-induced fresh catalysts were excellent to convert CO and the corresponding aged ones exhibited higher activities for the elimination of all the target pollutants. Among the aged catalysts, P2-a (the mole ratio of Pt/CA is 2:1) presented the best performance. Particularly, compared with the reference sample (Pc-a), the light-off temperatures (T50) of NO, HC and CO for P2-a decreased by 39 °C, 42 °C and 72 °C, respectively, and the full-conversion temperatures (T90) of NO, HC and CO for P2-a decreased by 44 °C, 44 °C and 48 °C, respectively. Therefore, this work provides a facile and valid method to manufacture advanced catalysts for purification of the vehicle exhaust in the future.

  17. Phenylbutyric acid induces the cellular senescence through an Akt/p21{sup WAF1} signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hag Dong [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Chang-Young [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Choe, Jeong Min [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Sohn, Jeongwon, E-mail: biojs@korea.ac.kr [Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Kim, Joon, E-mail: joonkim@korea.ac.kr [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Phenylbutyric acid induces cellular senescence. Black-Right-Pointing-Pointer Phenylbutyric acid activates Akt kinase. Black-Right-Pointing-Pointer The knockdown of PERK also can induce cellular senescence. Black-Right-Pointing-Pointer Akt/p21{sup WAF1} pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21{sup WAF1} induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21{sup WAF1} pathway by PERK inhibition.

  18. The Effect of Gallic Acid on Histopathologic Evaluation of Cerebellum in Valproic Acid-Induced Autism Animal Models

    Directory of Open Access Journals (Sweden)

    Parvin Samimi

    2016-06-01

    Full Text Available Autism spectrum disorder (ASD is counted as a worldwide public health problem. The possible causes of ASD are reactive oxygen species and free radicals. So, this study is aimed to evaluate the effects of Gallic acid, as an effective antioxidant, on histopathologic disorder of the cerebellum in valproic acid-induced autism animal models. 30 pregnant female rats were randomly divided into 5 groups, including: control, autism (or VAP and experimental 1, 2 and 3. Using a gavage needle, Gallic acid administered orally until about2 months of age. After the end of the treatment period, the rats were anesthetized with ether and their cerebellar tissues were removed for histopathologic studies. A significant decrease in the number of Purkinje and granular cells was observed in this study in VAP group compared to the control group (P≤0.05. A trend toward improvement was observed in the groups received 100 and 200 mg/kg of Gallic acid (P≤0.05. The results of this research revealed that Gallic acid reduces the side effects caused by valproic acid on cerebellar tissue of autistic rats. So, it should be considered for therapeutic goals.

  19. Quantitative volumetric analysis of a retinoic acid induced hypoplastic model of chick thymus, using Image-J.

    Science.gov (United States)

    Haque, Ayesha; Khan, Muhammad Yunus

    2017-09-01

    To assess the total volume change in a retinoic acid-induced, hypoplastic model of a chick thymus using Image-J. This experimental study was carried out at the anatomy department of College of Physicians and Surgeons, Islamabad, Pakistan, from February 2009 to February 2010, and comprised fertilised chicken eggs. The eggs were divided into experimental group A and control group C. Group A was injected with 0.3µg of retinoic acid via yolk sac to induce a defective model of a thymus with hypoplasia. The chicks were sacrificed on embryonic day 15 and at hatching. The thymus of each animal was processed, serially sectioned and stained. The total area of each section of thymus was calculated using Image-J. This total area was summed and multiplied with the thickness of each section to obtain volume. Of the 120 eggs, there were 60(50%) in each group. Image analysis revealed a highly significant decrease in the volume of the chick thymus in the experimental group A than its matched control at the time of hatching (p=0.001). Moreover, volumetric depletion progressed with time, being substantially pronounced at hatching compared to the embryonic stage. The volume changes were significant and were effectively quantified using Image-J.

  20. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury.

    Science.gov (United States)

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W; Flanders, Kathleen C; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M; Gonzalez, Frank J

    2012-12-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohistochemistry revealed higher TGFβ expression around the portal vein after LCA exposure and diminished SMAD3 phosphorylation in hepatocytes from Smad3-null mice. Serum metabolomics indicated increased bile acids and decreased lysophosphatidylcholine (LPC) after LCA exposure. Interestingly, in Smad3-null mice, the metabolic alteration was attenuated. LCA-induced lysophosphatidylcholine acyltransferase 4 (LPCAT4) and organic solute transporter β (OSTβ) expression were markedly decreased in Smad3-null mice, whereas TGFβ induced LPCAT4 and OSTβ expression in primary mouse hepatocytes. In addition, introduction of SMAD3 enhanced the TGFβ-induced LPCAT4 and OSTβ expression in the human hepatocellular carcinoma cell line HepG2. In conclusion, considering that Smad3-null mice showed attenuated serum ALP activity, a diagnostic indicator of cholangiocyte injury, these results strongly support the view that TGFβ-SMAD3 signaling mediates an alteration in phospholipid and bile acid metabolism following hepatic inflammation with the biliary injury.

  1. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity. (c) 2010 Elsevier B.V. All rights reserved.

  2. Preemptive hemodynamic intervention restricting the administration of fluids attenuates lung edema progression in oleic acid-induced lung injury.

    Science.gov (United States)

    Gil Cano, A; Gracia Romero, M; Monge García, M I; Guijo González, P; Ruiz Campos, J

    2017-04-01

    A study is made of the influence of preemptive hemodynamic intervention restricting fluid administration upon the development of oleic acid-induced lung injury. A randomized in vivo study in rabbits was carried out. University research laboratory. Sixteen anesthetized, mechanically ventilated rabbits. Hemodynamic measurements obtained by transesophageal Doppler signal. Respiratory mechanics computed by a least square fitting method. Lung edema assessed by the ratio of wet weight to dry weight of the right lung. Histological examination of the left lung. Animals were randomly assigned to either the early protective lung strategy (EPLS) (n=8) or the early protective hemodynamic strategy (EPHS) (n=8). In both groups, lung injury was induced by the intravenous infusion of oleic acid (OA) (0.133mlkg -1 h -1 for 2h). At the same time, the EPLS group received 15mlkg -1 h -1 of Ringer lactate solution, while the EPHS group received 30mlkg -1 h -1 . Measurements were obtained at baseline and 1 and 2h after starting OA infusion. After 2h, the cardiac index decreased in the EPLS group (pedema was greater in the EPHS group (pedema progression was attenuated by preemptively restricting the administration of fluids. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  3. Effect of marine mangrove Avicennia marina (Forssk.) Vierh against acetic acid-induced ulcerative colitis in experimental mice.

    Science.gov (United States)

    Rise, C L Victoria; Prabhu, V Vinod; Guruvayoorappan, Chandrasekharan

    2012-01-01

    Ulcerative colitis and Crohn's disease are two conditions that have many features in common and are referred as inflammatory bowel disease (IBD). Patients with IBD are predisposed to colorectal cancer. This investigation evaluates the effect of marine mangrove Avicennia marina against acetic acid-induced colitis. The treatment of A marina extract significantly decreased the colonic lipid peroxides, glutathione peroxidase, and serum nitric oxide and significantly increased the colonic and erythrocyte superoxide dismutase and glutathione levels compared with colitis control. In addition, A marina extract significantly decreased the lesion score and wet colon weight compared with colitis control. Treatment with A marina extract reflects its therapeutic activity against UC by minimal damage of colonic epithelial cells compared with colitis control during histopathologic examination. These protective role of A marina extract against UC could be attributed to the presence of higher levels of decanoic acid, diethylhydroxylamine (DEHA), pentanoic acid, pyrrolidine, 4-chlorophenyl, thiazolidinones, and arabinopyranoside (flavonoid). These findings suggest that A marina extract could be useful as a potential (natural) therapeutic agent for IBD.

  4. Simulation of biological therapies for degenerated intervertebral discs.

    Science.gov (United States)

    Zhu, Qiaoqiao; Gao, Xin; Temple, H Thomas; Brown, Mark D; Gu, Weiyong

    2016-04-01

    The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2017-07-15

    Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

  7. Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

    Science.gov (United States)

    Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D

    2017-03-20

    Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

  9. Phonon emission in a degenerate semiconductor at low lattice temperatures

    International Nuclear Information System (INIS)

    Midday, S.; Nag, S.; Bhattacharya, D.P.

    2015-01-01

    The characteristics of phonon growth in a degenerate semiconductor at low lattice temperatures have been studied for inelastic interaction of non-equilibrium electrons with the intravalley acoustic phonons. The energy of the phonon and the full form of the phonon distribution are taken into account. The results reveal significant changes in the growth characteristics compared to the same for a non-degenerate material

  10. Posterior Lattice Degeneration Characterized by Spectral Domain Optical Tomography

    OpenAIRE

    Manjunath, Varsha; Taha, Mohammed; Fujimoto, James G.; Duker, Jay S.

    2011-01-01

    PURPOSE: To utilize high-resolution spectral domain optical coherence tomography (SD-OCT) in the characterization of retinal and vitreal morphological changes overlying posterior lattice degeneration. METHODS: A cross-sectional, retrospective analysis was performed on 13 eyes of 13 nonconsecutive subjects with posterior lattice degeneration seen at the New England Eye Center, Tufts Medical Center between October 2009 and January 2010. SD-OCT images taken through the region of latti...

  11. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Ning-Ning Song

    2017-06-01

    Full Text Available The central serotonin (5-HT system is the main target of selective serotonin reuptake inhibitors (SSRIs, the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1 mice with altered central 5-HT levels from embryonic stages, (2 mice with deletion of 5-HT receptors from embryonic stages, and (3 mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal neurogenesis and its associated effects on depression.

  12. Cannabinoids modulate hippocampal memory and plasticity.

    Science.gov (United States)

    Abush, Hila; Akirav, Irit

    2010-10-01

    Considerable evidence demonstrates that cannabinoid agonists impair whereas cannabinoid antagonists improve memory and plasticity. However, recent studies suggest that the effects of cannabinoids on learning do not necessarily follow these simple patterns, particularly when emotional memory processes are involved. We investigated the involvement of the cannabinoid system in hippocampal learning and plasticity using the fear-related inhibitory avoidance (IA) and the non-fear-related spatial learning paradigms, and cellular models of learning and memory, i.e., long-term potentiation (LTP) and long-term depression (LTD). We found that microinjection into the CA1 of the CB1/CB2 receptor agonist WIN55,212-2 (5 μg/side) and an inhibitor of endocannabinoid reuptake and breakdown AM404 (200 ng/side) facilitated the extinction of IA, while the CB1 receptor antagonist AM251 (6 ng/side) impaired it. WIN55,212-2 and AM251 did not affect IA conditioning, while AM404 enhanced it, probably due to a drug-induced increase in pain sensitivity. However, in the water maze, systemic or local CA1 injections of AM251, WIN55,212-2, and AM404 all impaired spatial learning. We also found that i.p. administration of WIN55,212-2 (0.5 mg/kg), AM404 (10 mg/kg), and AM251 (2 mg/kg) impaired LTP in the Schaffer collateral-CA1 projection, whereas AM404 facilitated LTD. Our findings suggest diverse effects of the cannabinoid system on CA1 memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect of cannabinoid activation and deactivation, respectively. Moreover, they provide preclinical support for the suggestion that targeting the endocannabinoid system may aid in the treatment of disorders associated with impaired extinction-like processes, such as post-traumatic stress disorder. © 2009 Wiley-Liss, Inc.

  13. Sampling the Mouse Hippocampal Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Lisa Basler

    2017-12-01

    Full Text Available Sampling is a critical step in procedures that generate quantitative morphological data in the neurosciences. Samples need to be representative to allow statistical evaluations, and samples need to deliver a precision that makes statistical evaluations not only possible but also meaningful. Sampling generated variability should, e.g., not be able to hide significant group differences from statistical detection if they are present. Estimators of the coefficient of error (CE have been developed to provide tentative answers to the question if sampling has been “good enough” to provide meaningful statistical outcomes. We tested the performance of the commonly used Gundersen-Jensen CE estimator, using the layers of the mouse hippocampal dentate gyrus as an example (molecular layer, granule cell layer and hilus. We found that this estimator provided useful estimates of the precision that can be expected from samples of different sizes. For all layers, we found that a smoothness factor (m of 0 generally provided better estimates than an m of 1. Only for the combined layers, i.e., the entire dentate gyrus, better CE estimates could be obtained using an m of 1. The orientation of the sections impacted on CE sizes. Frontal (coronal sections are typically most efficient by providing the smallest CEs for a given amount of work. Applying the estimator to 3D-reconstructed layers and using very intense sampling, we observed CE size plots with m = 0 to m = 1 transitions that should also be expected but are not often observed in real section series. The data we present also allows the reader to approximate the sampling intervals in frontal, horizontal or sagittal sections that provide CEs of specified sizes for the layers of the mouse dentate gyrus.

  14. Mixed neurotransmission in the hippocampal mossy fibers

    Directory of Open Access Journals (Sweden)

    Agnieszka eMuenster-Wandowski

    2013-11-01

    Full Text Available The hippocampal mossy fibers (MFs, the axons of the granule cells of the dentate gyrus, innervate mossy cells and interneurons in the hilus on its way to CA3 where they innervate interneurons and pyramidal cells. Synapses on each target cell have distinct anatomical and functional characteristics. In recent years, the paradigmatic view of the MF synapses being only glutamatergic and, thus, excitatory has been questioned. Several laboratories have provided data supporting the hypothesis that the MFs can transiently release GABA during development and, in the adult, after periods of enhanced excitability. This transient glutamate-GABA co-transmission coincides with the transient expression of the machinery for the synthesis and release of GABA in the glutamatergic granule cells. Although some investigators have deemed this evidence controversial, new data has appeared with direct evidence of co-release of glutamate and GABA from single, identified MF boutons. However, this must still be confirmed by other groups and with other methodologies. A second, intriguing observation is that MF activation produced fast spikelets followed by excitatory postsynaptic potentials in a number of pyramidal cells, which, unlike the spikelets, underwent frequency potentiation and were strongly depressed by activation of metabotropic glutamate receptors. The spikelets persisted during blockade of chemical transmission and were suppressed by the gap junction blocker carbenoxolone. These data is consistent with the hypothesis of mixed electrical-chemical synapses between MFs and some pyramidal cells. Dye coupling between these types of principal cells and ultrastructural studies showing the co-existence of AMPA receptors and connexin 36 in this synapse corroborate their presence. A deeper consideration of mixed neurotransmission taking place in this synapse may expand our search and understanding of communication channels between different regions of the mammalian CNS.

  15. Gene expression profile analysis of human intervertebral disc degeneration

    Directory of Open Access Journals (Sweden)

    Kai Chen

    2013-01-01

    Full Text Available In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and f-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration.

  16. Risk of retinal detachment in patients with lattice degeneration.

    Science.gov (United States)

    Sasaki, K; Ideta, H; Yonemoto, J; Tanaka, S; Hirose, A; Oka, C

    1998-01-01

    To determine the risk of retinal detachment in patients with lattice degeneration of the retina, we statistically analyzed the incidence of retinal detachment in these patients. The data of hospital patients with retinal detachment associated with lattice degeneration in Kumamoto Prefecture, Japan, in 1990 were collected. The prevalence of lattice degeneration in Kumamoto was reported to be 9.5% in 1980. Based on population data from the 1990 census, the cumulative incidence of retinal detachment associated with lattice degeneration was calculated in this study. Among 1,840,000 residents in Kumamoto, there were 110 patients with retinal detachment associated with lattice degeneration; 72 with detachment resulting from tractional tears (tears), and 38 with detachment from atrophic holes. The cumulative incidence of retinal detachment from atrophic holes was 1.5% at the age of 40 years; from tears it was 3.6% at the age of 80 years. The cumulative incidence of detachment from both atrophic holes and tears was 5.3% at the age of 80 years. The results of this study are useful for clarifying the natural course of lattice degeneration.

  17. Posterior lattice degeneration characterized by spectral domain optical coherence tomography.

    Science.gov (United States)

    Manjunath, Varsha; Taha, Mohammed; Fujimoto, James G; Duker, Jay S

    2011-03-01

    The purpose of this study was to use high-resolution spectral domain optical coherence tomography in the characterization of retinal and vitreal morphological changes overlying posterior lattice degeneration. A cross-sectional retrospective analysis was performed on 13 eyes of 13 nonconsecutive subjects with posterior lattice degeneration seen at the New England Eye Center, Tufts Medical Center between October 2009 and January 2010. Spectral domain optical coherence tomography images taken through the region of lattice degeneration were qualitatively analyzed. Four characteristic changes of the retina and vitreous were seen in the 13 eyes with lattice degeneration: 1) anterior/posterior U-shaped vitreous traction; 2) retinal breaks; 3) focal retinal thinning; and 4) vitreous membrane formation. The morphologic appearance of vitreous traction and retinal breaks were found to be consistent with previous histologic reports. It is possible to image posterior lattice degeneration in many eyes using spectral domain optical coherence tomography and to visualize the spectrum of retinal and vitreous changes throughout the area of lattice degeneration.

  18. Nonlinear propagation of ion-acoustic waves in a degenerate dense ...

    Indian Academy of Sciences (India)

    both non-relativistic and ultrarelativistic limits. Therefore, in this paper, we consider a degenerate dense plasma containing non-relativistic degenerate cold ion fluid and both non-relativistic and ultrarelativistic degenerate electrons for studying the basic features of solitary waves in such a degenerate dense plasma.

  19. Bilateral reorganization of the dentate gyrus in hippocampal sclerosis

    Science.gov (United States)

    Thom, M; Martinian, L; Catarino, C; Yogarajah, M; Koepp, M J.; Caboclo, L; Sisodiya, S M.

    2009-01-01

    Background: Hippocampal sclerosis (HS) is the most common surgical pathology associated with mesial temporal lobe epilepsy (MTLE). HS is typically characterized by mossy fiber sprouting (MFS) and reorganization of neuropeptide Y (NPY) fiber networks in the dentate gyrus. One potential cause of postoperative seizure recurrence following temporal lobe surgery may be the presence of seizure-associated bilateral hippocampal damage. We aimed to investigate patterns of hippocampal abnormalities in a postmortem series as identified by NPY and dynorphin immunohistochemistry. Methods: Analysis of dentate gyrus fiber reorganization, using dynorphin (to demonstrate MFS) and NPY immunohistochemistry, was carried out in a postmortem epilepsy series of 25 cases (age range 21–96 years). In 9 patients, previously refractory seizures had become well controlled for up to 34 years prior to death. Results: Bilateral MFS or abnormal NPY patterns were seen in 15 patients including those with bilateral symmetric, asymmetric, and unilateral HS by conventional histologic criteria. MFS and NPY reorganization was present in all classical HS cases, more variably in atypical HS, present in both MTLE and non-MTLE syndromes and with seizure histories of up to 92 years, despite seizure remission in some patients. Conclusion: Synaptic reorganization in the dentate gyrus may be a bilateral, persistent process in epilepsy. It is unlikely to be sufficient to generate seizures and more likely to represent a seizure-induced phenomenon. GLOSSARY AED = antiepileptic drug; CA1p = CA1-predominant hippocampal sclerosis; CHS = classical hippocampal sclerosis; EFG = end folium gliosis; EFS = end folium sclerosis; GCD = granule cell dispersion; GCL = granule cell layer; HS = hippocampal sclerosis; MFS = mossy fiber sprouting; MTLE = mesial temporal lobe epilepsy; NPY = neuropeptide Y; ROI = region of interest; SE = status epilepticus; TLE = temporal lobe epilepsy. PMID:19710404

  20. Roles of hippocampal subfields in verbal and visual episodic memory.

    Science.gov (United States)

    Zammit, Andrea R; Ezzati, Ali; Zimmerman, Molly E; Lipton, Richard B; Lipton, Michael L; Katz, Mindy J

    2017-01-15

    Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, pmemory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Higher-order conditioning is impaired by hippocampal lesions.

    Science.gov (United States)

    Gilboa, Asaf; Sekeres, Melanie; Moscovitch, Morris; Winocur, Gordon

    2014-09-22

    Behavior in the real world is rarely motivated by primary conditioned stimuli that have been directly associated with potent unconditioned reinforcers. Instead, motivation and choice behavior are driven by complex chains of higher-order associations that are only indirectly linked to intrinsic reward and often exert their influence outside awareness. Second-order conditioning (SOC) [1] is a basic associative-learning mechanism whereby stimuli acquire motivational salience by proxy, in the absence of primary incentives [2, 3]. Memory-systems theories consider first-order conditioning (FOC) and SOC to be prime examples of hippocampal-independent nondeclarative memory [4, 5]. Accordingly, neurobiological models of SOC focus almost exclusively on nondeclarative neural systems that support motivational salience and reward value. Transfer of value from a conditioned stimulus to a neutral stimulus is thought to require the basolateral amygdala [6, 7] and the ventral striatum [2, 3], but not the hippocampus. We developed a new paradigm to measure appetitive SOC of tones in rats. Hippocampal lesions severely impaired both acquisition and expression of SOC despite normal FOC. Unlike controls, rats with hippocampal lesions could not discriminate between positive and negative secondary conditioned tones, although they exhibited general familiarity with previously presented tones compared with new tones. Importantly, normal rats' behavior, in contrast to that of hippocampal groups, also revealed different confidence levels as indexed by effort, a central characteristic of hippocampal relational memory. The results indicate, contrary to current systems models, that representations of intrinsic relationships between reward value, stimulus identity, and motivation require hippocampal mediation when these relationships are of a higher order. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Modulation of hippocampal activity with fornix Deep Brain Stimulation.

    Science.gov (United States)

    Stypulkowski, Paul H; Stanslaski, Scott R; Giftakis, Jonathon E

    Deep Brain Stimulation (DBS) within the Papez circuit is under investigation as a treatment for epilepsy and Alzheimer's disease. We previously reported the effects of stimulation at nodes within this network (anterior thalamic nucleus and hippocampus) on hippocampal activity in a large animal model, using a chronic implantable, clinical-grade system that permits concurrent stimulation and recording. In this study we extended earlier work to compare the effects of fornix DBS on evoked potentials (EPs) and local field potential (LFP) activity within the hippocampus, and to assess closed-loop stimulation. Unilateral fornix and hippocampal DBS leads were implanted in three ovine subjects using image-guided, frameless stereotaxy. Chronic, awake recordings of EPs and LFPs in response to fornix and hippocampal stimulation were collected with the implanted device and analyzed off-line. Stimulation of the fornix produced robust, short latency hippocampal EPs. High frequency fornix stimulation generated parameter-dependent effects. At low amplitudes, short lasting inhibition of LFP activity occurred. Above a specific amplitude threshold, DBS elicited pronounced bursts of theta activity, followed by a marked state shift in hippocampal activity. These effects persisted for minutes post-DBS and were reflected as changes in LFP spectral content and phase-amplitude coupling. Real-time modulation of hippocampal activity via the implanted device was demonstrated using LFPs as the control signal for closed-loop stimulation. The current results expand earlier findings and demonstrate target-specific effects produced by DBS within this neural circuit. These changes in network activity may provide insights into stimulation targets and parameter selection for clinical investigations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  4. Perceptual learning in patients with macular degeneration

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    Tina ePlank

    2014-10-01

    Full Text Available Patients with age-related macular degeneration (AMD or hereditary macular dystrophies (JMD rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT at their preferred retinal locus (PRL used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later took part in three functional magnetic resonance imaging (fMRI sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p=.001 in the stimulus onset asynchrony (SOA between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p=.014. The following trends were observed: (i Improvement in Vernier acuity for an eccentric line-bisection task; (ii positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r=0.531; (iii positive correlation between the increase in task performance and initial fixation stability (r=0.730. The first two trends were non-significant, whereas the third trend was significant at p=.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

  5. Frontotemporal Lobar Degeneration and microRNAs

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    Paola ePiscopo

    2016-02-01

    Full Text Available Frontotemporal lobar degeneration (FTLD includes a spectrum of disorders characterized by changes of personality and social behaviour and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly miRNAs. Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107 and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD.

  6. Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting

    Science.gov (United States)

    Yau, Suk-yu; Li, Ang; So, Kwok-Fai

    2015-01-01

    Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting. PMID:26380120

  7. MPTP-meditated hippocampal dopamine deprivation modulates synaptic transmission and activity-dependent synaptic plasticity

    International Nuclear Information System (INIS)

    Zhu Guoqi; Chen Ying; Huang Yuying; Li Qinglin; Behnisch, Thomas

    2011-01-01

    Parkinson's disease (PD)-like symptoms including learning deficits are inducible by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, it is possible that MPTP may disturb hippocampal memory processing by modulation of dopamine (DA)- and activity-dependent synaptic plasticity. We demonstrate here that intraperitoneal (i.p.) MPTP injection reduces the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) within 7 days. Subsequently, the TH expression level in SN and hippocampus and the amount of DA and its metabolite DOPAC in striatum and hippocampus decrease. DA depletion does not alter basal synaptic transmission and changes pair-pulse facilitation (PPF) of field excitatory postsynaptic potentials (fEPSPs) only at the 30 ms inter-pulse interval. In addition, the induction of long-term potentiation (LTP) is impaired whereas the duration of long-term depression (LTD) becomes prolonged. Since both LTP and LTD depend critically on activation of NMDA and DA receptors, we also tested the effect of DA depletion on NMDA receptor-mediated synaptic transmission. Seven days after MPTP injection, the NMDA receptor-mediated fEPSPs are decreased by about 23%. Blocking the NMDA receptor-mediated fEPSP does not mimic the MPTP-LTP. Only co-application of D1/D5 and NMDA receptor antagonists during tetanization resembled the time course of fEPSP potentiation as observed 7 days after i.p. MPTP injection. Together, our data demonstrate that MPTP-induced degeneration of DA neurons and the subsequent hippocampal DA depletion alter NMDA receptor-mediated synaptic transmission and activity-dependent synaptic plasticity. - Highlights: → I.p. MPTP-injection mediates death of dopaminergic neurons. → I.p. MPTP-injection depletes DA and DOPAC in striatum and hippocampus. → I.p. MPTP-injection does not alter basal synaptic transmission. → Reduction of LTP and enhancement of LTD after i.p. MPTP-injection. → Attenuation of NMDA-receptors mediated

  8. Risk factors of age-related macular degeneration in Argentina

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    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  9. Structure of stable degeneration of K3 surfaces into pairs of rational elliptic surfaces

    OpenAIRE

    Kimura, Yusuke

    2018-01-01

    F-theory/heterotic duality is formulated in the stable degeneration limit of a K3 fibration on the F-theory side. In this note, we analyze the structure of the stable degeneration limit. We discuss whether stable degeneration exists for pairs of rational elliptic surfaces. We demonstrate that, when two rational elliptic surfaces have an identical complex structure, stable degeneration always exists. We provide an equation that systematically describes the stable degeneration of a K3 surface i...

  10. Hippocampal N-methyl-d-aspartate and kainate binding in response to entorhinal cortex aspiration or 192 IgG-saporin lesions of the basal forebrain

    International Nuclear Information System (INIS)

    Gallagher, M.; Gill, T.M.; Shivers, A.; Nicolle, M.M.

    1997-01-01

    Lesion models in the rat were used to examine the effects of removing innervation of the hippocampal formation on glutamate receptor binding in that system. Bilateral aspiration of the entorhinal cortex was used to remove the cortical innervation of the hippocampal formation and the dentate gyrus. The subcortical input to the hippocampus from cholinergic neurons of the basal forebrain was lesioned by microinjection of the immunotoxin 192 IgG-saporin into the medial septum and vertical limb of diagonal band. After a 30-day postlesion survival, the effects of these lesions on N-methyl-d-aspartate-displaceable [ 3 H]glutamate and [ 3 H]kainate binding in the hippocampus were quantified using in vitro autoradiography. The bilateral entorhinal lesion induced a sprouting response in the dentate gyrus, measured by an increase in the width of [ 3 H]kainate binding. It also induced an increase in the density of [ 3 H]kainate binding in CA3 stratum lucidum and an increase in N-methyl-d-aspartate binding throughout the hippocampus proper and the dentate gyrus. The selective lesion of cholinergic septal input did not have any effect on hippocampal [ 3 H]kainate binding and induced only a moderate decrease in N-methyl-d-aspartate binding that was not statistically reliable.The entorhinal and cholinergic lesions were used as in vivo models of the degeneration of hippocampal input that occurs in normal aging and Alzheimer's disease. The results from the present lesion study suggest that some, but not all, of the effects on hippocampal [ 3 H]kainate and N-methyl-d-aspartate binding induced by the lesions are consistent with the status of binding to these receptors in aging and Alzheimer's disease. Consistent with the effects of aging and Alzheimer's disease is an altered topography of [ 3 H]kainate binding after entorhinal cortex lesion and a modest decline in N-methyl-d-aspartate binding after lesions of the cholinergic septal input to the hippocampus. (Copyright (c) 1997

  11. Photoperiod is associated with hippocampal volume in a large community sample.

    Science.gov (United States)

    Miller, Megan A; Leckie, Regina L; Donofry, Shannon D; Gianaros, Peter J; Erickson, Kirk I; Manuck, Stephen B; Roecklein, Kathryn A

    2015-04-01

    Although animal research has demonstrated seasonal changes in hippocampal volume, reflecting seasonal neuroplasticity, seasonal differences in human hippocampal volume have yet to be documented. Hippocampal volume has also been linked to depressed mood, a seasonally varying phenotype. Therefore, we hypothesized that seasonal differences in day-length (i.e., photoperiod) would predict differences in hippocampal volume, and that this association would be linked to low mood. Healthy participants aged 30-54 (M=43; SD=7.32) from the University of Pittsburgh Adult Health and Behavior II project (n=404; 53% female) were scanned in a 3T MRI scanner. Hippocampal volumes were determined using an automated segmentation algorithm using FreeSurfer. A mediation model tested whether hippocampal volume mediated the relationship between photoperiod and mood. Secondary analyses included seasonally fluctuating variables (i.e., sleep and physical activity) which have been shown to influence hippocampal volume. Shorter photoperiods were significantly associated with higher BDI scores (R(2)=0.01, β=-0.12, P=0.02) and smaller hippocampal volumes (R(2)=0.40, β=0.08, P=0.04). However, due to the lack of an association between hippocampal volume and Beck Depression Inventory scores in the current sample, the mediation hypothesis was not supported. This study is the first to demonstrate an association between season and hippocampal volume. These data offer preliminary evidence that human hippocampal plasticity could be associated with photoperiod and indicates a need for longitudinal studies. © 2014 Wiley Periodicals, Inc.

  12. Tyro3 Modulates Mertk-Associated Retinal Degeneration.

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    Douglas Vollrath

    2015-12-01

    Full Text Available Inherited photoreceptor degenerations (IPDs are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6 allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129 modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL, with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis

  13. Genetic association studies in lumbar disc degeneration: a systematic review.

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    Pasi J Eskola

    Full Text Available Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI in humans.A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines.Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576.Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

  14. Mitochondrial proteomics of the acetic acid - induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii - derived hybrid strain

    Science.gov (United States)

    Guerreiro, Joana F.; Sampaio-Marques, Belém; Soares, Renata; Coelho, Ana V.; Leão, Cecília; Ludovico, Paula; Sá-Correia, Isabel

    2016-01-01

    Very high concentrations of acetic acid at low pH induce programmed cell death (PCD) in both the experimental model Saccharomyces cerevisiae and in Zygosaccharomyces bailii, the latter being considered the most problematic acidic food spoilage yeast due to its remarkable intrinsic resistance to this food preservative. However, while the mechanisms underlying S. cerevisiae PCD induced by acetic acid have been previously examined, the corresponding molecular players remain largely unknown in Z. bailii. Also, the reason why acetic acid concentrations known to be necrotic for S. cerevisiae induce PCD with an apoptotic phenotype in Z. bailii remains to be elucidated. In this study, a 2-DE-based expression mitochondrial proteomic analysis was explored to obtain new insights into the mechanisms involved in PCD in the Z. bailii derived hybrid strain ISA1307. This allowed the quantitative assessment of expression of protein species derived from each of the parental strains, with special emphasis on the processes taking place in the mitochondria known to play a key role in acetic acid - induced PCD. A marked decrease in the content of proteins involved in mitochondrial metabolism, in particular, in respiratory metabolism (Cor1, Rip1, Lpd1, Lat1 and Pdb1), with a concomitant increase in the abundance of proteins involved in fermentation (Pdc1, Ald4, Dld3) was registered. Other differentially expressed identified proteins also suggest the involvement of the oxidative stress response, protein translation, amino acid and nucleotide metabolism, among other processes, in the PCD response. Overall, the results strengthen the emerging concept of the importance of metabolic regulation of yeast PCD. PMID:28357336

  15. Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Xia, Jingen; Zhang, Heng; Sun, Bing; Yang, Rui; He, Hangyong; Zhan, Qingyuan

    2014-06-01

    It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

  16. Priming by Hexanoic acid induce activation of mevalonic and linolenic pathways and promotes the emission of plant volatiles.

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    Eugenio eLlorens

    2016-04-01

    Full Text Available Hexanoic acid is a short natural monocarboxylic acid present in some fruits and plants. Previous studies reported that soil drench application of this acid induces effective resistance in tomato plants against Botrytis cinerea and Pseudomonas syringae and in citrus against Alternaria alternata and Xanthomonas citri. In this work, we performed an in deep study of the metabolic changes produced in citrus by the application of hexanoic acid in response to the challenge pathogen Alternaria alternata, focusing on the response of the plant. Moreover, we used 13C labeled hexanoic to analyze its behavior inside the plants. Finally, we studied the volatile emission of the treated plants after the challenge inoculation. Drench application of 13C labeled hexanoic demonstrated that this molecule stays in the roots and is not mobilized to the leaves, suggesting long distance induction of resistance. Moreover, the study of the metabolic profile showed an alteration of more than two hundred molecules differentially induced by the application of the compound and the inoculation with the fungus. Bioinformatics analysis of data showed that most of these altered molecules could be related with the mevalonic and linolenic pathways suggesting the implication of these pathways in the induced resistance mediated by hexanoic acid. Finally, the application of this compound showed an enhancement of the emission of 17 volatile metabolites. Taken together, this study indicates that after the application of hexanoic acid this compound remains in the roots, provoking molecular changes that may trigger the defensive response in the rest of the plant mediated by changes in the mevalonic and linolenic pathways and enhancing the emission of volatile compounds, suggesting for the first time the implication of mevalonic pathway in response to hexanoic application.

  17. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.

    Science.gov (United States)

    Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Koike, Marcia Kiyomi; Cintra, Dennys Esper; Ferreira, Fabiana Dias; Nunes, Valeria Sutti; Castilho, Gabriela; Gioielli, Luiz Antonio; Paula Bombo, Renata; Catanozi, Sergio; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Passarelli, Marisa; Nakandakare, Edna Regina; Lottenberg, Ana Maria

    2016-06-01

    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism

    Science.gov (United States)

    Kim, Ji-Woon; Seung, Hana; Kwon, Kyung Ja; Ko, Mee Jung; Lee, Eun Joo; Oh, Hyun Ah; Choi, Chang Soon; Kim, Ki Chan; Gonzales, Edson Luck; You, Jueng Soo; Choi, Dong-Hee; Lee, Jongmin; Han, Seol-Heui; Yang, Sung Min; Cheong, Jae Hoon; Shin, Chan Young; Bahn, Geon Ho

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance. PMID:25133713

  19. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

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    Mohsen Minaiyan

    2014-02-01

    Full Text Available Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE and its chloroform fraction (MCF on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4% and continued for 5 days. Prednisolone (4 mg/kg and normal saline (1 ml/kg were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6 and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive.

  20. The Healing Effect of Hydroalcoholic Extract of Hypericum Perforatum on Acetic Acid-Induced Ulcerative Colitis in Male Rats

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    Nader Tanideh

    2017-02-01

    Full Text Available Background & Objective: Anti-inflammatory effect of Hypericum have long been considered. Ulcerative Colitis (UC is a form of Inflammatory Bowel Disease (IBD. In this study, the effects of Hypericum perforatum on histopathological changes and tissue malondialdehyde (MDA level of colonic tissue in rats with induced UC were evaluated. Materials & Methods: 70 rats were divided into seven equal groups. Colitis was induced by acetic acid.. Groups I and II received 1 mL of 600 and 300 mg/kg H. perforatum extract orally per day respectively; groups III and IV received 1 mL of 20% and 10% intra-colonic gel form of H. perforatum extract daily respectively; group V, as positive control, received 1 mL of intra-colonic Asacol; group VI received 1 mL of normal saline as negative control; group VII received just intra-colonic gel base. All the animals were evaluated for histological changes and tissue MDA level of colon seven days after the treatment. Results: H. perforatum extract in the two forms of trans-rectal and oral administration could result in a more healing effect on acetic acid-induced damaged colonic tissue with a reduction in the MDA activity. In trans-rectal administration, the 20% gel had a better healing response than the 10% gel. In oral administration, the 600 mg/kg dosage had a better healing response than the 300 mg/kg. Conclusions: Therefor, H. perforatum can be considered as a treatment of choice for UC especially in trans-rectal gel form.

  1. Comparative gastroprotective effects of natural honey, nigella sativa and cimetidine against acetylsalicylic acid Induced gastric ulcer in albino rats

    International Nuclear Information System (INIS)

    Bukhari, M.H.; Khalil, J.; Zahid, M.; Ansari, N.

    2011-01-01

    Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines. (author)

  2. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    Directory of Open Access Journals (Sweden)

    F Aura Kullmann

    Full Text Available Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5% to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion was precisely repeated every 30 minutes. Administration of vehicle (saline i.v. occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v. after the 8(th. Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function.

  3. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome.

    Science.gov (United States)

    Carmona-Mora, Paulina; Encina, Carolina A; Canales, Cesar P; Cao, Lei; Molina, Jessica; Kairath, Pamela; Young, Juan I; Walz, Katherina

    2010-08-25

    Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1. We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity. Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.

  4. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1 mutations associated with Smith-Magenis Syndrome

    Directory of Open Access Journals (Sweden)

    Carmona-Mora Paulina

    2010-08-01

    Full Text Available Abstract Background Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1. Little is known about the function of human RAI1. Results We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end were able to localize into the nucleus but had no transactivation activity. Conclusion Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.

  5. Participation of nuclear factor (erythroid 2-related), factor 2 in ameliorating lithocholic acid-induced cholestatic liver injury in mice.

    Science.gov (United States)

    Tan, K P; Wood, G A; Yang, M; Ito, S

    2010-11-01

    Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA-induced toxicity in vivo. Nrf2 disrupted (Nrf2(-/-) ) and wild-type mice were treated with LCA (125 mg·kg(-1) body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined. In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S-transferases, haeme oxygenase-1 and multidrug resistance-associated proteins 3 and 4 in the wild type as compared with the Nrf2(-/-) mice. Moreover, basal and LCA-induced hepatic glutathione and activities of glutathione S-transferases and thioredoxin reductases were higher in wild-type than in Nrf2(-/-) mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2(-/-) mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase. Nrf2 plays a crucial cytoprotective role against LCA-induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

  6. Diagnosis problems of paraneoplastic cerebellar degeneration

    Directory of Open Access Journals (Sweden)

    N.A. Shnaider

    2014-01-01

    Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare form of the paraneoplastic neurological syndrome (PNS. PCD is an autoimmune disease of the central nervous system (CNS affecting the Purkinje cells and possibly other cells of the cerebellum. PCD is characterized by a rapid onset resulting in disability for a few days or weeks; a slow progredient increase in cerebellar symptomatology is observed less often. PCD develops in 1–3% of cancer patients; its fraction accounts for 25% of all forms of PNS. The mean incidence rate of PCD is about 2 cases per 1,000 cancer patients. PCD develops in patients with cancer of the ovary, uterus and fallopian tubes, with small cell lung cancer and Hodgkin's lymphoma. The incidence rate among females is 3 times higher than that among males. Females aged 50–65 years are most likely to suffer from PCD. PCDs are divided into four main subgroups that differ in terms of prognosis and range of associated antineuronal antibodies. In the last decade, different classes of anti-onconeuronal antibodies associated with PCD have been described; 9 of them have been best studied. Anti-Yo and anti-Hu antibodies are most frequently detected upon PCD. PCD can be also diagnosed without anti-onconeuronal antibodies associated with it or their titer in the blood can be low. Differential diagnosis of PCD is complex and is conducted for a wide range of CNS diseases. No single approach to treating PCD currently exists. Surgical removal of the tumor, the source of production of anti-onconeuronal antigens, followed by radiotherapy and/or chemotherapy, does not solve the problem completely, but may reduce severity of the clinical manifestations of PCD or stabilize the pathological process. This explains the need for rapid and profound search for a tumor in patients suspected with PCD. The authors described a clinical case of an acute debut of PCD in 47-year-old female, 6 months after which, the patient was diagnosed with breast

  7. Magnetic resonance imaging of corticobasal degeneration

    International Nuclear Information System (INIS)

    Ozaki, Yutaka; Maehara, Tadayuki; Izawa, Nana; Suzuki, Michimasa; Komura, Shinji; Nakanishi, Atsushi

    2005-01-01

    The purpose of this paper is to clarify the frequency of each magnetic resonance (MR) finding in corticobasal degeneration (CBD) patients, and to evaluate correlations between the predominant side of MR findings and the most affected side of cortical dysfunction and extrapyramidal symptoms. In 30 patients with clinically diagnosed CBD, MR images were reviewed retrospectively. Two experienced neuroradiologists evaluated previously reported MR findings of CBD (cortical atrophy, subcortical high intensity on T2WI, ventricular dilatation, atrophy of basal ganglia, high or low intensity of basal ganglia on T2WI, and atrophy of corpus callosum) using a 4 step-scale (absent, mild, moderate, and severe). Asymmetrical changes in the cortex and basal ganglia were also evaluated. A neurologist reviewed clinical records of all 30 patients and determined the most affected side of cortical dysfunction and extrapyramidal symptoms. Cortical atrophy was observed in all 30 CBD patients (mild=10, moderate=14, severe=6), particularly at paracentral region (17/30), frontotemporal lobe (6/30), and whole cerebrum (7/30). Other findings such as subcortical high intensity on T2WI (n=11), ventricular dilatation (n=26), atrophy of basal ganglia (n=16), high or low intensity of putamen on T2WI (n=15) were also observed. Asymmetrical atrophic and/or intensity changes were seen in cortex (n=26) and basal ganglia (n=13). Atrophy of corpus callosum was observed in 10 out of the 19 patients who underwent sagittal imaging, and was limited to the middle of corpus callosum. In 16 patients with predominantly left-sided body symptoms due to cortical dysfunction, MR images showed right dominant (n=12) or symmetrical (n=4) cortical atrophy. All 13 patients with predominantly right body symptoms due to cortical dysfunction showed left dominant cortical atrophy on MR images. In 13 patients with predominantly left body extrapyramidal symptoms, MR images showed right dominant (n=3), symmetrical (n=4), or no

  8. Dancing or Fitness Sport? The Effects of Two Training Programs on Hippocampal Plasticity and Balance Abilities in Healthy Seniors

    Directory of Open Access Journals (Sweden)

    Kathrin Rehfeld

    2017-06-01

    Full Text Available Age-related degenerations in brain structure are associated with balance disturbances and cognitive impairment. However, neuroplasticity is known to be preserved throughout lifespan and physical training studies with seniors could reveal volume increases in the hippocampus (HC, a region crucial for memory consolidation, learning and navigation in space, which were related to improvements in aerobic fitness. Moreover, a positive correlation between left HC volume and balance performance was observed. Dancing seems a promising intervention for both improving balance and brain structure in the elderly. It combines aerobic fitness, sensorimotor skills and cognitive demands while at the same time the risk of injuries is low. Hence, the present investigation compared the effects of an 18-month dancing intervention and traditional health fitness training on volumes of hippocampal subfields and balance abilities. Before and after intervention, balance was evaluated using the Sensory Organization Test and HC volumes were derived from magnetic resonance images (3T, MP-RAGE. Fourteen members of the dance (67.21 ± 3.78 years, seven females, and 12 members of the fitness group (68.67 ± 2.57 years, five females completed the whole study. Both groups revealed hippocampal volume increases mainly in the left HC (CA1, CA2, subiculum. The dancers showed additional increases in the left dentate gyrus and the right subiculum. Moreover, only the dancers achieved a significant increase in the balance composite score. Hence, dancing constitutes a promising candidate in counteracting the age-related decline in physical and mental abilities.

  9. PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.

    Science.gov (United States)

    Wu, Liping; Oshima, Tadayuki; Shan, Jing; Sei, Hiroo; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2015-10-15

    Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1, and ASICs. Copyright © 2015 the American Physiological Society.

  10. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury[S

    OpenAIRE

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W.; Flanders, Kathleen C.; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M.; Gonzalez, Frank J.

    2012-01-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohisto...

  11. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    Science.gov (United States)

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Cranial Radiation Therapy and Damage to Hippocampal Neurogenesis

    Science.gov (United States)

    Monje, Michelle

    2008-01-01

    Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic…

  13. Endurance Factors Improve Hippocampal Neurogenesis and Spatial Memory in Mice

    Science.gov (United States)

    Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette

    2011-01-01

    Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor [delta] agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and…

  14. Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

    Directory of Open Access Journals (Sweden)

    Edit Frankó

    Full Text Available Alzheimer's disease (AD is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

  15. Impaired Odor Recognition Memory in Patients with Hippocampal Lesions

    Science.gov (United States)

    Levy, Daniel A.; Squire, Larry R.; Hopkins, Ramona O.

    2004-01-01

    In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be…

  16. Remodeling of Hippocampal Synapses After Hippocampus-Dependent Associative Learning

    NARCIS (Netherlands)

    Geinisman, Yuri; Disterhoft, John F.; Gundersen, Hans Jørgen G.; McEchron, Matthew D.; Persina, Inna S.; Power, John M.; Zee, Eddy A. van der; West, Mark J.

    2000-01-01

    The aim of this study was to determine whether hippocampus-dependent associative learning involves changes in the number and/or structure of hippocampal synapses. A behavioral paradigm of trace eyeblink conditioning was used. Young adult rabbits were given daily 80 trial sessions to a criterion of

  17. Inhibition of hippocampal synaptic transmission by impairment of Ral function

    DEFF Research Database (Denmark)

    Owe-Larsson, Björn; Chaves-Olarte, Esteban; Chauhan, Ashok

    2005-01-01

    Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ra...

  18. Depression may be associated with hippocampal volume changes ...

    African Journals Online (AJOL)

    Adele

    pression whereas there was no relationship between cumulative time treated with antidepressants during depression.31. The HPA Axis in Depression. The HPA axis and its vulnerability to stress may be the common fac- tor in the hippocampal atrophy and associated memory deficits seen in depression and other disorders ...

  19. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

    Science.gov (United States)

    Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

    2017-08-01

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

    Science.gov (United States)

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M

    2016-03-01

    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p atrophy (p = 0.001, p = 0.023), and ventricular expansion (p atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Input from the medial septum regulates adult hippocampal neurogenesis

    NARCIS (Netherlands)

    Van der Borght, Karin; Mulder, Jan; Keijser, Jan N; Eggen, Bart J L; Luiten, Paul G.M.; Van der Zee, Eddy A; Keijser, Johannes

    2005-01-01

    Neural progenitors in the subgranular zone of the hippocampal formation form a continuously proliferating cell population, generating new granule neurons throughout adult life. Between 10 days and 1 month after their formation, many of the newly generated cells die. The present study investigated

  2. Classical Conditioning of Hippocampal Theta Patterns in the Rat.

    Science.gov (United States)

    1976-08-01

    associated with changes in performance of learned tasks , 1,4,5, 8,9 there have been very few studies of neurona l plasticity of the hippocampus It self...rapid development of a conditioned hippocampal theta response to a visual sti mulus demonstrates tha t there is considerable neurona l plasticity in the

  3. Increased hippocampal-prefrontal functional connectivity in insomnia

    NARCIS (Netherlands)

    Leerssen, Jeanne; Wassing, Rick; Ramautar, Jennifer R; Stoffers, Diederick; Lakbila-Kamal, Oti; Perrier, Joy; Bruijel, Jessica; Foster-Dingley, Jessica C; Aghajani, Moji; van Someren, Eus J W

    2018-01-01

    Insomnia Disorder (ID) is the second-most common mental disorder and has a far-reaching impact on daytime functioning. A meta-analysis indicates that, of all cognitive domains, declarative memory involving the hippocampus is most affected in insomnia. Hippocampal functioning has consistently been

  4. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico...

  5. Hippocampal development in youth with a history of childhood maltreatment.

    Science.gov (United States)

    Paquola, Casey; Bennett, Maxwell R; Hatton, Sean N; Hermens, Daniel F; Groote, Inge; Lagopoulos, Jim

    2017-08-01

    Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14-28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2014-01-01

    Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

  7. Amnesia due to bilateral hippocampal glioblastoma. MRI finding

    Energy Technology Data Exchange (ETDEWEB)

    Shimauchi, M.; Wakisaka, S.; Kinoshita, K. (Miyazaki Medical Coll., Kiyotake (Japan). Dept. of Neurosurgery)

    1989-11-01

    The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a 'butterfly' lesion, it is unusual for it to invade the limbic system selectively to this extent. (orig.).

  8. Anticonvulsant and neuroprotective effects of the novel calcium antagonist NP04634 on kainic acid-induced seizures in rats.

    Science.gov (United States)

    Morales-Garcia, Jose A; Luna-Medina, Rosario; Martinez, Ana; Santos, Angel; Perez-Castillo, Ana

    2009-12-01

    Kainic acid (KA)-induced status epilepticus (SE) is a well-characterized model of excitotoxic neuronal injury. Excitotoxicity results from activation of specific glutamate receptors, with resultant elevation of intracellular Ca(2+). The CA1 and CA3 subregions of the hippocampus are especially vulnerable to KA, and this pattern of neuronal injury resembles that occurring in patients with temporal lobe epilepsy. Calcium plays an essential role in excitotoxicity, and accordingly calcium channel inhibitors have been shown to have protective effects in various experimental models of epilepsy and brain injury. Moreover, they also potentiate the antiseizure efficacy of conventional antiepileptic drugs. This study was undertaken to determine whether NP04634, a novel compound, reported as a non-L-type voltage-sensitive calcium channel (VSCC) inhibitor, could prevent the entrance in SE and the neuronal loss evoked by intraperitoneal injection of KA. Our results show that intragastrical administration of NP04634 reduced the percentage of rats that entered SE after KA injection, increased the latency of SE entry, and significantly reduced the mortality of rats that entered SE. Also, NP04634 prevented the loss of hippocampal CA1 and CA3 pyramidal neurons and reduced the gliosis induced by KA. These results point to a potential anticonvulsant and neuroprotective role for NP04634. Copyright 2009 Wiley-Liss, Inc.

  9. Proteomic analysis of the effect of acupuncture on the suppression of kainic Acid-induced neuronal destruction in mouse hippocampus.

    Science.gov (United States)

    Bae, Chang-Hwan; Kim, Dong-Soo; Jun, Ye Lee; Kwon, Sunoh; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2013-01-01

    Kainic acid (KA) is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20-25 g) received acupuncture treatment at HT8 acupoint bilaterally once a day for 3 days and were then administered KA (30 mg/kg) intraperitoneally. Twenty-four hours after KA injection, neuronal survival and astrocyte activation in the hippocampus were measured, and protein expression in the hippocampus was identified by 2-dimensional electrophoresis. Acupuncture stimulation at HT8 suppressed KA-induced neuronal death and astrocyte activation in the hippocampus. We identified the changes in the expression of 11 proteins by KA or acupuncture stimulation at HT8 and found that acupuncture stimulation at HT8 normalized the expression of dihydropyrimidinase-related protein 2 and upregulated the expression of transcriptional activator protein pur-alpha, serine/threonine-protein phosphatase 5, and T-complex protein 1 subunit alpha, which are related to the survival of neurons. These results suggest that acupuncture stimulation at HT8 changes protein expression profiles in the hippocampus in favor of neuronal survival in KA-treated mice.

  10. Proteomic Analysis of the Effect of Acupuncture on the Suppression of Kainic Acid-Induced Neuronal Destruction in Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Chang-Hwan Bae

    2013-01-01

    Full Text Available Kainic acid (KA is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20–25 g received acupuncture treatment at HT8 acupoint bilaterally once a day for 3 days and were then administered KA (30 mg/kg intraperitoneally. Twenty-four hours after KA injection, neuronal survival and astrocyte activation in the hippocampus were measured, and protein expression in the hippocampus was identified by 2-dimensional electrophoresis. Acupuncture stimulation at HT8 suppressed KA-induced neuronal death and astrocyte activation in the hippocampus. We identified the changes in the expression of 11 proteins by KA or acupuncture stimulation at HT8 and found that acupuncture stimulation at HT8 normalized the expression of dihydropyrimidinase-related protein 2 and upregulated the expression of transcriptional activator protein pur-alpha, serine/threonine-protein phosphatase 5, and T-complex protein 1 subunit alpha, which are related to the survival of neurons. These results suggest that acupuncture stimulation at HT8 changes protein expression profiles in the hippocampus in favor of neuronal survival in KA-treated mice.

  11. Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway.

    Science.gov (United States)

    Rezayat, Seyed Mahdi; Dehpour, Ahmad-Reza; Motamed, Saeed Mohammadi; Yazdanparast, Maryam; Chamanara, Mohsen; Sahebgharani, Mousa; Rashidian, Amir

    2017-10-24

    The aim of the present study is to investigate the protective effects of Foeniculum vulgare essential oil on intestinal inflammation through the inhibition of NF-kB pathway in acetic acid-induced rat colitis. Acute colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid (4%) solution. Two hours after the induction of colitis, 0.2% tween 80 in normal saline, dexamethasone (2 mg/kg) and F. vulgare essential oil (100, 200, 400 mg/kg) were administered to the animals by oral gavage and continued for 5 consecutive days. Assessment of macroscopic and microscopic lesions was done. MPO activity was evaluated by biochemical method. Furthermore, TNF-α activity was detected by immunohistochemistry (IHC) and the expression level of p-NF-kB p65 protein was measured by western blot analysis. Dexamethasone and F. vulgare essential oil (200, 400 mg/kg) reduced the macroscopic and microscopic lesions compared to the acetic acid group (p acetic acid group. Furthermore, they inhibited acetic acid-induced expression of p-NF-kB p65 protein (p acetic acid-induced colitis in rats may involve the inhibition of NF-kB pathway.

  12. Correlation between intervertebral disc degeneration, paraspinal muscle atrophy, and lumbar facet joints degeneration in patients with lumbar disc herniation.

    Science.gov (United States)

    Sun, Dong; Liu, Peng; Cheng, Jie; Ma, Zikun; Liu, Jingpei; Qin, Tingzheng

    2017-04-20

    To assess the correlation between lumbar disc degeneration (LDD), multifidus muscle atrophy (LMA), and facet joints degeneration in patients with L4-L5 lumbar disc herniation (LDH). Sixty patients with L4-L5 LDH diagnosed by a 1.5 T MRI scanner were enrolled in the study group and another 60 patients with non-specific back pain were enrolled in the control group. LDD, LMA, and facet joints degeneration were examined and analyzed independently by two independent orthopedic surgeons using T2-weighted images. Wilcoxon test was used for analyzing the difference of LDD and facet joints degeneration between L3-L4 and L5-S1 and difference of LMA between the herniated and control groups. Correlation analysis of the three degeneration grades at the same level was determined by Spearman rank correlation test. In the herniated group, most LMA at L3-L4 level was grade 1 (42, 70.0%); grade 2 (33, 55.0%) at L4-L5 level; and grade 3 (27, 45.0%) at L5-S1 level. LMA and LDD grading were significantly different between L3-L4 and L5-S1 levels (P herniation group, the Spearman value for LDD and LMA grading were 0.352 (P  0.05) at the L5-S1 level. The differences in LMA between the herniated and control groups at the three levels were significant (P Disc degeneration and multifidus muscles atrophy were positively correlated at the L3-L4 disc level. A lumbar extension muscle strengthening program could be helpful in preventing muscle atrophy and lumbar spinal degeneration.

  13. Deficiency of adaptive immunity does not interfere with Wallerian degeneration.

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    Christopher R Cashman

    Full Text Available Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.

  14. LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

    Science.gov (United States)

    Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

    2016-12-01

    To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

  15. Notochord Cells in Intervertebral Disc Development and Degeneration

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    Matthew R. McCann

    2016-01-01

    Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

  16. Nicotinamide adenine dinucleotide replenishment rescues colon degeneration in aged mice.

    Science.gov (United States)

    Zhu, Xudong; Shen, Weiyan; Wang, Ying; Jaiswal, Amit; Ju, Zhenyu; Sheng, Qinsong

    2017-01-01

    Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration. A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms. Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide (NAD) level in aged mice. Compared to 3-month-old young controls, 2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation. Despite upregulated colonic tryptophan hydroxylases expression, serotonin release and expression of colon-predominant type IV serotonin receptor, reduced viability of interstitial cells of Cajal while enhanced aquaporins (Aqp1, 3 and 11) led to a less colonic motility and increased luminal dehydration in aged mice. Notably, this colonic degeneration was accompanied with reduced key NAD + -generating enzyme expression and lowered NAD + /NADH ratio in aged colon. Three-month continuous administration of beta nicotinamide mononucleotide, a NAD + precursor, elevated colonic NAD + level and improved defecation in aged mice. In contrast, pharmacological inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme for NAD + biosynthesis, induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice. Taken together, these findings suggest the beneficial effect of NAD + in maintaining colonic homoeostasis and reactivating NAD + biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.

  17. Hippocampal sleep features: relations to human memory function

    Directory of Open Access Journals (Sweden)

    Michele eFerrara

    2012-04-01

    Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

  18. Vitamin D and hippocampal development-the story so far.

    Directory of Open Access Journals (Sweden)

    Anne L Lardner

    2015-10-01

    Full Text Available Epidemiological studies suggest that vitamin D insufficiency may be prevalent in young as well as older populations. The pleiotropic effects of vitamin D are now beyond dispute and a growing number of studies provide accumulating evidence of a role for vitamin D in brain development and function. A number of studies to date have investigated the effects of early-life vitamin D deprivation on adult hippocampus in animals and humans, and there is a growing body of evidence to suggest a role for this hormone in the development of selected hippocampal functions such as latent inhibition and hole board habituation in rats. There are few studies to date of vitamin D deprivation or supplementation on early hippocampal development in vivo. However, a small number of studies, mostly in vitro, point to a role for vitamin D in differentiation and development of hippocampal neurons. There is also limited evidence that supplementation with vitamin D following a period of deprivation is capable of restoring cellular activity and later function. Further avenues of future research are outlined including animal studies on the effects of vitamin D deprivation and inadequacy on early hippocampal biochemistry and function e.g. measurement of BDNF levels, GABAergic activity, long-term potentiation and spatial navigation,. It also remains to be established if there are critical developmental windows during which vitamin D is required. In light of the importance of the hippocampus in LTP and spatial learning, further investigations on the early effects of vitamin D deprivation on hippocampal development are warranted

  19. Dedicated Hippocampal Inhibitory Networks for Locomotion and Immobility.

    Science.gov (United States)

    Arriaga, Moises; Han, Edward B

    2017-09-20

    Network activity is strongly tied to animal movement; however, hippocampal circuits selectively engaged during locomotion or immobility remain poorly characterized. Here we examined whether distinct locomotor states are encoded differentially in genetically defined classes of hippocampal interneurons. To characterize the relationship between interneuron activity and movement, we used in vivo , two-photon calcium imaging in CA1 of male and female mice, as animals performed a virtual-reality (VR) track running task. We found that activity in most somatostatin-expressing and parvalbumin-expressing interneurons positively correlated with locomotion. Surprisingly, nearly one in five somatostatin or one in seven parvalbumin interneurons were inhibited during locomotion and activated during periods of immobility. Anatomically, the somata of somatostatin immobility-activated neurons were smaller than those of movement-activated neurons. Furthermore, immobility-activated interneurons were distributed across cell layers, with somatostatin-expressing cells predominantly in stratum oriens and parvalbumin-expressing cells mostly in stratum pyramidale. Importantly, each cell's correlation between activity and movement was stable both over time and across VR environments. Our findings suggest that hippocampal interneuronal microcircuits are preferentially active during either movement or immobility periods. These inhibitory networks may regulate information flow in "labeled lines" within the hippocampus to process information during distinct behavioral states. SIGNIFICANCE STATEMENT The hippocampus is required for learning and memory. Movement controls network activity in the hippocampus but it's unclear how hippocampal neurons encode movement state. We investigated neural circuits active during locomotion and immobility and found interneurons were selectively active during movement or stopped periods, but not both. Each cell's response to locomotion was consistent across time

  20. Micro-MRI study of cerebral aging: ex vivo detection of hippocampal sub-field reorganization, micro-hemorrhages and amyloid plaques in mouse lemur primates

    International Nuclear Information System (INIS)

    Bertrand, Anne; Petiet, Alexandra; Dhenain, Marc; Pasquier, Adrien; Kraska, Audrey; Joseph-Mathurin, Nelly; Wiggins, Christopher; Aujard, Fabienne; Mestre-Frances, Nadine

    2013-01-01

    Mouse lemurs are non-human primate models of cerebral aging and neuro-degeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 μm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral micro-hemorrhages. (authors)

  1. Hippocampal EEG and behaviour in dog. III. Hippocampal EEG correlates of stimulus-response tasks and of sexual behaviour

    NARCIS (Netherlands)

    Arnolds, D.E.A.T.; Lopes da Silva, F.H.; Aitink, J.W.; Kamp, A.

    A dog was trained to perform a spatial sound discrimination. The hippocampal EEG correlates and the movement correlates of correct trials were compared with those of incorrect trials and of ‘pressings in between’. Correct and wrong responses on a place learning task were compared both with

  2. Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain

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    María I. Herrera

    2018-03-01

    Full Text Available Perinatal asphyxia (PA is an obstetric complication associated with an impaired gas exchange. This health problem continues to be a determinant of neonatal mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA has exerted neuroprotection in several models of brain injury and neurodegeneration. We aimed at evaluating the potential neuroprotective role of PEA in an experimental model, which induces PA in the immature rat brain. PA was induced by placing Sprague Dawley newborn rats in a water bath at 37°C for 19 min. Once their physiological conditions improved, they were given to surrogate mothers that had delivered normally within the last 24 h. The control group was represented by non-fostered vaginally delivered pups, mimicking the clinical situation. Treatment with PEA (10 mg/kg was administered within the first hour of life. Modifications in the hippocampus were analyzed with conventional electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP and western blot (for pNF H/M, MAP-2, and GFAP. Behavior was also studied throughout Open Field (OF Test, Passive Avoidance (PA Task and Elevated Plus Maze (EPM Test. After 1 month of the PA insult, we observed neuronal nucleus degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing the level of expression of these markers by western blot. Vertical exploration impairments and anxiety-related behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-induced hippocampal damage and its corresponding behavioral alterations. These results contribute to the elucidation of PEA neuroprotective role after PA and the future establishment of therapeutic strategies for the developing brain.

  3. Genome-wide identification of genes involved in the positive and negative regulation of acetic acid-induced programmed cell death in Saccharomyces cerevisiae.

    Science.gov (United States)

    Sousa, Marlene; Duarte, Ana Marta; Fernandes, Tânia R; Chaves, Susana R; Pacheco, Andreia; Leão, Cecília; Côrte-Real, Manuela; Sousa, Maria João

    2013-11-28

    Acetic acid is mostly known as a toxic by-product of alcoholic fermentation carried out by Saccharomyces cerevisiae, which it frequently impairs. The more recent finding that acetic acid triggers apoptotic programmed cell death (PCD) in yeast sparked an interest to develop strategies to modulate this process, to improve several biotechnological applications, but also for biomedical research. Indeed, acetate can trigger apoptosis in cancer cells, suggesting its exploitation as an anticancer compound. Therefore, we aimed to identify genes involved in the positive and negative regulation of acetic acid-induced PCD by optimizing a functional analysis of a yeast Euroscarf knock-out mutant collection. The screen consisted of exposing the mutant strains to acetic acid in YPD medium, pH 3.0, in 96-well plates, and subsequently evaluating the presence of culturable cells at different time points. Several functional categories emerged as greatly relevant for modulation of acetic acid-induced PCD (e.g.: mitochondrial function, transcription of glucose-repressed genes, protein synthesis and modifications, and vesicular traffic for protection, or amino acid transport and biosynthesis, oxidative stress response, cell growth and differentiation, protein phosphorylation and histone deacetylation for its execution). Known pro-apoptotic and anti-apoptotic genes were found, validating the approach developed. Metabolism stood out as a main regulator of this process, since impairment of major carbohydrate metabolic pathways conferred resistance to acetic acid-induced PCD. Among these, lipid catabolism arose as one of the most significant new functions identified. The results also showed that many of the cellular and metabolic features that constitute hallmarks of tumour cells (such as higher glycolytic energetic dependence, lower mitochondrial functionality, increased cell division and metabolite synthesis) confer sensitivity to acetic acid-induced PCD, potentially explaining why

  4. Degenerate Fermi gas in a combined harmonic-lattice potential

    International Nuclear Information System (INIS)

    Blakie, P. B.; Bezett, A.; Buonsante, P.

    2007-01-01

    In this paper we derive an analytic approximation to the density of states for atoms in a combined optical lattice and harmonic trap potential as used in current experiments with quantum degenerate gases. We compare this analytic density of states to numerical solutions and demonstrate its validity regime. Our work explicitly considers the role of higher bands and when they are important in quantitative analysis of this system. Applying our density of states to a degenerate Fermi gas, we consider how adiabatic loading from a harmonic trap into the combined harmonic-lattice potential affects the degeneracy temperature. Our results suggest that occupation of excited bands during loading should lead to more favorable conditions for realizing degenerate Fermi gases in optical lattices

  5. Peripheral retinal degenerations and the risk of retinal detachment.

    Science.gov (United States)

    Lewis, Hilel

    2003-07-01

    To review the degenerative diseases of the peripheral retina in relationship with the risk to develop a rhegmatogenous retinal detachment and to present recommendations for use in eyes at increased risk of developing a retinal detachment. Focused literature review and author's clinical experience. Retinal degenerations are common lesions involving the peripheral retina, and most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic therapy; however, adequate studies have not been performed to date. Well-designed, prospective, randomized clinical studies are necessary to determine the benefit-risk ratio of prophylactic treatment. In the meantime, the evidence available suggests that most of the peripheral retinal degenerations should not be treated except in rare, high-risk situations.

  6. Rapid glutamate receptor 2 trafficking during retinal degeneration

    Directory of Open Access Journals (Sweden)

    Lin Yanhua

    2012-02-01

    Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

  7. [Myopia: frequency of lattice degeneration and axial length].

    Science.gov (United States)

    Martín Sánchez, M D; Roldán Pallarés, M

    2001-05-01

    To evaluate the relationship between lattice retinal degeneration and axial length of the eye in different grades of myopia. A sample of 200 eyes from 124 myopic patients was collected by chance. The average age was 34.8 years (20-50 years) and the myopia was between 0.5 and 20 diopters (D). The eyes were grouped according to the degree of refraction defect, the mean axial length of each group (Scan A) and the frequency of lattice retinal degeneration and the relationship between these variables was studied. The possible influence of age on our results was also considered. For the statistical analysis, the SAS 6.07 program with the variance analysis for quantitative variables, and chi(2) test for qualitative variables with a 5% significance were used. A multivariable linear regression model was also adjusted. The highest frequency of lattice retinal degeneration occurred in those myopia patients having more than 15 D, and also in the group of myopia patients between 3 and 6 D, but this did not show statistical significance when compared with the other myopic groups. If the axial length is assessed, a greater frequency of lattice retinal degeneration is also found when the axial length is 25-27 mm and 29-30 mm, which correspond, respectively, to myopias between 3-10 D and more than 15 D. When the multivariable linear regression model was adjusted, the axial length showed the existence of lattice retinal degeneration (beta 0.41 mm; p=0.08) adjusted by the number of diopters (beta 0.38 mm; plattice retinal degeneration was found for myopias with axial eye length between 29-30 mm (more than 15 D), and 25-27 mm (between 3-10 D).

  8. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus

    Science.gov (United States)

    Shukitt-Hale, Barbara; Lau, Francis C.; Carey, Amanda N.; Galli, Rachel L.; Spangler, Edward L.; Ingram, Donald K.; Joseph, James A.

    2016-01-01

    Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study, we investigated whether polyphenols in blueberries can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1β and TNF-α, the neurotrophic factor IGF-1, and the transcription factor NF-κB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1β, TNF-α, and NF-κB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions

  9. Wallerian degeneration of the corticospinal tract in the brain stem

    International Nuclear Information System (INIS)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato

    1989-01-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T 2 -weighted images - with or without decreased signal intensities in axial T 1 -weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T 1 -weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author)

  10. PHOTORECEPTOR DEGENERATION IN A MOUNTAIN LION CUB (PUMA CONCOLOR).

    Science.gov (United States)

    DiSalvo, Andrew R; Reilly, Christopher M; Wiggans, K Tomo; Woods, Leslie W; Wack, Ray F; Clifford, Deana L

    2016-12-01

    An orphaned 4-mo-old female mountain lion cub ( Puma concolor ) was captured along the coastline in Montaña de Oro State Park in Los Osos, California, USA. Following suspicion that the cub was visually impaired, ophthalmic examination revealed diffuse bilateral retinal atrophy. Due to a poor prognosis, humane euthanasia was elected. Necropsy and histopathological findings were consistent with photoreceptor degeneration. Based on the cub's signalment, history, and histopathology, a genetic or nutritional etiology was suspected, with the former etiology more strongly supported. To the authors' knowledge, this is the first report of photoreceptor degeneration in a wild felid and should be considered in cases of blindness.

  11. Relationship between retinal lattice degeneration and open angle glaucoma.

    Science.gov (United States)

    Rahimi, Mansour

    2005-01-01

    Patients with retinal disorders may develop glaucoma of both a primary and secondary type. Pigment may contribute to trabecular obstruction in some patients with open-angle glaucoma. Lattice degeneration of the retina in its typical form is a sharply demarcated, circumferentially oriented, degenerative process with significant alterations of retinal pigmentation. The association between myopia, open angle glaucoma and pigment dispersion is striking. Therefore, it could be postulated that there is significant prevalence of open angle glaucoma in patients with retinal lattice degeneration, especially in combination with myopia.

  12. Automated imaging dark adaptometer for investigating hereditary retinal degenerations

    Science.gov (United States)

    Azevedo, Dario F. G.; Cideciyan, Artur V.; Regunath, Gopalakrishnan; Jacobson, Samuel G.

    1995-05-01

    We designed and built an automated imaging dark adaptometer (AIDA) to increase accuracy, reliability, versatility and speed of dark adaptation testing in patients with hereditary retinal degenerations. AIDA increases test accuracy by imaging the ocular fundus for precise positioning of bleaching and stimulus lights. It improves test reliability by permitting continuous monitoring of patient fixation. Software control of stimulus presentation provides broad testing versatility without sacrificing speed. AIDA promises to facilitate the measurement of dark adaptation in studies of the pathophysiology of retinal degenerations and in future treatment trials of these diseases.

  13. Design of the Advanced Virgo non-degenerate recycling cavities

    International Nuclear Information System (INIS)

    Granata, M; Barsuglia, M; Flaminio, R; Freise, A; Hild, S; Marque, J

    2010-01-01

    Advanced Virgo is the project to upgrade the interferometric gravitational wave detector Virgo, and it foresees the implementation of power and signal non-degenerate recycling cavities. Such cavities suppress the build-up of high order modes of the resonating sidebands, with some advantage for the commissioning of the detector and the build-up of the gravitational signal. Here we present the baseline design of the Advanced Virgo non-degenerate recycling cavities, giving some preliminary results of simulations about the tolerances of this design to astigmatism, mirror figure errors and thermal lensing.

  14. Maximum principles for boundary-degenerate linear parabolic differential operators

    OpenAIRE

    Feehan, Paul M. N.

    2013-01-01

    We develop weak and strong maximum principles for boundary-degenerate, linear, parabolic, second-order partial differential operators, $Lu := -u_t-\\tr(aD^2u)-\\langle b, Du\\rangle + cu$, with \\emph{partial} Dirichlet boundary conditions. The coefficient, $a(t,x)$, is assumed to vanish along a non-empty open subset, $\\mydirac_0!\\sQ$, called the \\emph{degenerate boundary portion}, of the parabolic boundary, $\\mydirac!\\sQ$, of the domain $\\sQ\\subset\\RR^{d+1}$, while $a(t,x)$ may be non-zero at po...

  15. The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory.

    Science.gov (United States)

    Rodrigue, Karen M; Daugherty, Ana M; Haacke, E Mark; Raz, Naftali

    2013-07-01

    The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity--volume and iron concentration--and the associated age differences in memory performance. In 113 healthy adults (age 19-83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation times, and assessed memory performance with multiple tests. We applied structural equation modeling to evaluate the contribution of individual differences in 2 indices of integrity, volume and T2*, to age-related memory variance. The results show that in healthy adults, age differences in memory can be explained in part by individual differences in HC volume that in turn are associated with differences in HC iron concentration. Lower memory scores were linked to smaller HC and higher HC iron concentration. No such associations were noted for Cd and VC. We conclude that the association between age-related declines in memory and reduced hippocampal volume may reflect the impact of oxidative stress related to increase in free iron concentration. Longitudinal follow-up is needed to test whether altered iron homeostasis in the HC is an early marker for age-related cognitive decline.

  16. Hippocampal Damage Increases Deontological Responses during Moral Decision Making.

    Science.gov (United States)

    McCormick, Cornelia; Rosenthal, Clive R; Miller, Thomas D; Maguire, Eleanor A

    2016-11-30

    Complex moral decision making is associated with the ventromedial prefrontal cortex (vmPFC) in humans, and damage to this region significantly increases the frequency of utilitarian judgments. Since the vmPFC has strong anatomical and functional links with the hippocampus, here we asked how patients with selective bilateral hippocampal damage would derive moral decisions on a classic moral dilemmas paradigm. We found that the patients approved of the utilitarian options significantly less often than control participants, favoring instead deontological responses-rejecting actions that harm even one person. Thus, patients with hippocampal damage have a strikingly opposite approach to moral decision making than vmPFC-lesioned patients. Skin-conductance data collected during the task showed increased emotional arousal in the hippocampal-damaged patients and they stated that their moral decisions were based on emotional instinct. By contrast, control participants made moral decisions based on the integration of an adverse emotional response to harming others, visualization of the consequences of one's action, and the rational re-evaluation of future benefits. This integration may be disturbed in patients with either hippocampal or vmPFC damage. Hippocampal lesions decreased the ability to visualize a scenario and its future consequences, which seemed to render the adverse emotional response overwhelmingly dominant. In patients with vmPFC damage, visualization might also be reduced alongside an inability to detect the adverse emotional response, leaving only the utilitarian option open. Overall, these results provide insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions. The ventromedial prefrontal cortex (vmPFC) is closely associated with the ability to make complex moral judgements. When this area is damaged, patients become more utilitarian (the ends justify the means) and have

  17. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France); Barbeau, Emmanuel J. [CNRS - Universite Paul Sabatier Toulouse 3, Centre de Recherche Cerveau et Cognition, UMR-5549, Toulouse (France); Didic, Mira; Poncet, Michel; Ceccaldi, Mathieu [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Felician, Olivier [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Centre Saint-Charles, Laboratoire de Neurobiologie Integrative et Adaptative, UMR CNRS 6149, Marseille (France); Laforte, Catherine de; Mundler, Olivier [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Ranjeva, Jean-Philippe; Cozzone, Patrick J. [Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France)

    2009-07-15

    Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the ''net sum'' of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. (orig.)

  18. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

    International Nuclear Information System (INIS)

    Guedj, Eric; Barbeau, Emmanuel J.; Didic, Mira; Poncet, Michel; Ceccaldi, Mathieu; Felician, Olivier; Laforte, Catherine de; Mundler, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick J.

    2009-01-01

    Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the ''net sum'' of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. (orig.)

  19. Modulation of Adult Hippocampal Neurogenesis by Sleep: Impact on Mental Health

    Directory of Open Access Journals (Sweden)

    Cristina Navarro-Sanchis

    2017-10-01

    Full Text Available The process of neurogenesis has been demonstrated to occur throughout life in the subgranular zone (SGZ of the hippocampal dentate gyrus of several mammals, including humans. The basal rate of adult hippocampal neurogenesis can be altered by lifestyle and environmental factors. In this perspective review, the evidence for sleep as a modulator of adult hippocampal neurogenesis is first summarized. Following this, the impacts of sleep and sleep disturbances on hippocampal-dependent functions, including learning and memory, and depression are critically evaluated. Finally, we postulate that the effects of sleep on hippocampal-dependent functions may possibly be mediated by a change in adult hippocampal neurogenesis. This could provide a route to new treatments for cognitive impairments and psychiatric disorders.

  20. Modulation of Adult Hippocampal Neurogenesis by Sleep: Impact on Mental Health

    Science.gov (United States)

    Navarro-Sanchis, Cristina; Brock, Olivier; Winsky-Sommerer, Raphaelle; Thuret, Sandrine

    2017-01-01

    The process of neurogenesis has been demonstrated to occur throughout life in the subgranular zone (SGZ) of the hippocampal dentate gyrus of several mammals, including humans. The basal rate of adult hippocampal neurogenesis can be altered by lifestyle and environmental factors. In this perspective review, the evidence for sleep as a modulator of adult hippocampal neurogenesis is first summarized. Following this, the impacts of sleep and sleep disturbances on hippocampal-dependent functions, including learning and memory, and depression are critically evaluated. Finally, we postulate that the effects of sleep on hippocampal-dependent functions may possibly be mediated by a change in adult hippocampal neurogenesis. This could provide a route to new treatments for cognitive impairments and psychiatric disorders. PMID:29075182

  1. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  2. Degenerate optimization problems of economics and power engineering

    International Nuclear Information System (INIS)

    Klimenko, A.V.

    2015-01-01

    Optimization of large economic and power engineering systems leads to degenerate solutions of high dimension. This is a very strong mathematical complication. However, the author emphasized that it allows to consider future development of the power industry based on simultaneous use of nuclear power plants (NPPs) together with coal- and gas power plants, or solely on NPPs [ru

  3. Cartilage Degeneration and Alignment in Severe Varus Knee Osteoarthritis.

    Science.gov (United States)

    Nakagawa, Yasuaki; Mukai, Shogo; Yabumoto, Hiromitsu; Tarumi, Eri; Nakamura, Takashi

    2015-10-01

    The aim of this study was to examine the relationship between cartilage, ligament, and meniscus degeneration and radiographic alignment in severe varus knee osteoarthritis in order to understand the development of varus knee osteoarthritis. Fifty-three patients (71 knees) with primary varus knee osteoarthritis and who underwent total knee arthroplasty were selected for this study. There were 6 men and 47 women, with 40 right knees and 31 left knees studied; their mean age at operation was 73.5 years. The ligament, meniscus, degeneration of joint cartilage, and radiographic alignments were examined visually. The tibial plateau-tibial shaft angle was larger if the condition of the cartilage in the lateral femoral condyle was worse. The femorotibial angle and tibial plateau-tibial shaft angle were larger if the conditions of the lateral meniscus or the cartilage in the lateral tibial plateau were worse. Based on the results of this study, progression of varus knee osteoarthritis may occur in the following manner: medial knee osteoarthritis starts in the central portion of the medial tibial plateau, and accompanied by medial meniscal extrusion and anterior cruciate ligament rupture, cartilage degeneration expands from the anterior to the posterior in the medial tibial plateau. Bone attrition occurs in the medial tibial plateau, and the femoro-tibial angle and tibial plateau-tibial shaft angle increase. Therefore, the lateral intercondylar eminence injures the cartilage of the lateral femoral condyle in the longitudinal fissure type. Thereafter, the cartilage degeneration expands in the whole of the knee joints.

  4. Current surgical treatment of age-related macular degeneration

    NARCIS (Netherlands)

    Ramos de Carvalho, J. Emanuel; Willig, A. J. H. E.; Chung, R.; Peiretti, E.; Mura, M.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe, irreversible central vision loss in individuals over 65 years of age throughout much of the developed world. The advent of anti-VEGF therapy has had a great impact in the long-term natural history of this condition, more

  5. Cesare Lombroso: an anthropologist between evolution and degeneration.

    Science.gov (United States)

    Mazzarello, Paolo

    2011-01-01

    Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration, a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the "born delinquent" whose development had stopped at an early stage, making them the most "atavistic" types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of "biological compensation" for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a heated debate on the biological determinism of human behaviour.

  6. Morphometric analyses of the visual pathways in macular degeneration

    NARCIS (Netherlands)

    Hernowo, Aditya T.; Prins, Doety; Baseler, Heidi A.; Plank, Tina; Gouws, Andre D.; Hooymans, Johanna M. M.; Morland, Antony B.; Greenlee, Mark W.; Cornelissen, Frans W.

    Introduction: Macular degeneration (MD) causes central visual field loss. When field defects occur in both eyes and overlap, parts of the visual pathways are no longer stimulated. Previous reports have shown that this affects the grey matter of the primary visual cortex, but possible effects on the

  7. Age-related macular degeneration in Onitsha, Nigeria | Nwosu ...

    African Journals Online (AJOL)

    Objectives: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. Materials and Methods: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed.

  8. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  9. Identification of Age-Related Macular Degeneration Using OCT Images

    Science.gov (United States)

    Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

    2018-02-01

    Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

  10. Spectral analysis of linear relations and degenerate operator semigroups

    International Nuclear Information System (INIS)

    Baskakov, A G; Chernyshov, K I

    2002-01-01

    Several problems of the spectral theory of linear relations in Banach spaces are considered. Linear differential inclusions in a Banach space are studied. The construction of the phase space and solutions is carried out with the help of the spectral theory of linear relations, ergodic theorems, and degenerate operator semigroups

  11. Rank equivalent and rank degenerate skew cyclic codes

    DEFF Research Database (Denmark)

    Martinez Peñas, Umberto

    2017-01-01

    Two skew cyclic codes can be equivalent for the Hamming metric only if they have the same length, and only the zero code is degenerate. The situation is completely different for the rank metric. We study rank equivalences between skew cyclic codes of different lengths and, with the aim of finding...

  12. A class of degenerate stochastic differential equations with non ...

    Indian Academy of Sciences (India)

    Introduction. In this article we consider (possibly degenerate) stochastic differential equations (SDEs) with non-Lipschitz coefficients. If the coefficients are Lipschitz, we can prove the existence of a unique strong solution (see [9]). But uniqueness fails in the case of non-Lipschitz coefficients. The literature on this topic is not ...

  13. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  14. Sequential changes in MR imaging of human wallerian degeneration

    International Nuclear Information System (INIS)

    Orita, Tetsuji; Tsurutani, Tohru; Izumihara, Akifumi; Kajiwara, Koji; Matsunaga, Tokio.

    1994-01-01

    MRI of wallerian degeneration of the pyramidal tract in the brainstem was repeatedly performed on the same coronal slice in 10 patients, who had infarction or hemorrhage of the basal ganglia and had the exact onset of hemiparesis. The processes of wallerian degeneration were divided into four stages by proton-density weighted images. In stage 1, the axon began to degenerate and was destroyed. It occurred during the first 0.7 month and resulted in no signal intensity abnormality. In stage 2, axon debris disappeared from degenerating tracts. Myelin structure was preserved and myelin lipid remained intact. The lipid water ratio in the tissue became large and the tissue was more hydrophobic. From 0.7 to 2.0 months, low signal intensity was observed. In stage 3, subsequent myelin lipid breakdown began and the lipid/water ratio in the tissue tended to be small. There was no abnormal signal intensity. In stage 4, lipid began to be removed from the tissue. The lipid/water ratio became smaller and the tissue became hydrophilic. Gliosis was more prominent. High signal intensity was observed. (author)

  15. Twisted mass lattice QCD with non-degenerate quark masses

    International Nuclear Information System (INIS)

    Muenster, Gernot; Sudmann, Tobias

    2006-01-01

    Quantum Chromodynamics on a lattice with Wilson fermions and a chirally twisted mass term is considered in the framework of chiral perturbation theory. For two and three numbers of quark flavours, respectively, with non-degenerate quark masses the pseudoscalar meson masses and decay constants are calculated in next-to-leading order including lattice effects quadratic in the lattice spacing a

  16. Treatment of dry age-related macular degeneration with dobesilate

    OpenAIRE

    Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

    2012-01-01

    The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture.

  17. Urocortin 2 treatment is protective in excitotoxic retinal degeneration.

    Science.gov (United States)

    Szabadfi, K; Kiss, P; Reglodi, D; Fekete, E M; Tamas, A; Danyadi, B; Atlasz, T; Gabriel, R

    2014-03-01

    Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

  18. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.

    Science.gov (United States)

    Berner, Andre K; Kleinman, Mark E

    2016-01-01

    Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina.

  19. The molecular genetic basis of age-related macular degeneration ...

    Indian Academy of Sciences (India)

    Keywords. AMD; epidemiology; genes; polymorphism; risk. Abstract. Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly.

  20. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  1. Nutritional modulation of age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  2. Parainflammation, chronic inflammation, and age-related macular degeneration.

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

  3. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  4. Therapeutic Potential of Statins in Age-related Macular Degeneration

    African Journals Online (AJOL)

    Age-related macular degeneration (ARMD) is the leading cause of irreversible vision loss, affecting one in three people aged 75 and above. Although exciting new pharmaceuticals to treat ARMD such as endothelial growth factor (VEGF) inhibitors, are now available, they are effective only in selected group of patients, and ...

  5. on visual acuity in age related macular degeneration

    African Journals Online (AJOL)

    marine origin) in the treatment of age related macular degeneration (AMD). In a randomized double blind clinical trial 280 eyes of 280 (157 F, 123 M) patients with wet and dry AMD were randomly assigned in treatment or placebo groups. Patients in ...

  6. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic...

  7. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Hoyng, Carel B.; Kersten, Eveline; Kilger, Ellen; Langen, Hanno; Lengyel, Imre; Luthert, Phil; Maugeais, Cyrille; Meester-Smoor, Magda; Monés, Jordi; Nogoceke, Everson; Peto, Tunde; Pool, Frances M.; Rodríguez, Eduardo; Ueffing, Marius; Ulrich Bartz-Schmidt, Karl U.; van Leeuwen, Elisabeth M.; Verzijden, Timo; Zumbansen, Markus; Acar, Niyazi; Anastosopoulos, Eleftherios; Azuara-Blanco, Augusto; Bergen, Arthur; Binquet, Christine; Bird, Alan; Brétillon, Lionel; Buitendijk, Gabrielle; Cachulo, Maria Luz; Chakravarthy, Usha; Chan, Michelle; Chang, Petrus; Colijn, Johanna; Cumberland, Philippa; Cunha-Vaz, José; Daien, Vincent; Deak, Gabor; Delyfer, Marie-Noëlle; den Hollander, Anneke; Dietzel, Martha; Erke, Maja Gran; Fauser, Sascha; Finger, Robert; Fletcher, Astrid; Foster, Paul; Founti, Panayiota; Göbel, Arno; Gorgels, Theo; Grauslund, Jakob; Grus, Franz; Hammond, Christopher; Helmer, Catherine; Hense, Hans-Werner; Hermann, Manuel; Hoehn, René; Hogg, Ruth; Holz, Frank; Hoyng, Carel; Jansonius, Nomdo; Janssen, Sarah; Khawaja, Anthony; Klaver, Caroline; Lamparter, Julia; Le Goff, Mélanie; Leal, Sergio; Lechanteur, Yara; Lehtimäki, Terho; Lotery, Andrew; Leung, Irene; Mauschitz, Matthias; Merle, Bénédicte; Meyer Zu Westrup, Verena; Midena, Edoardo; Miotto, Stefania; Mirshahi, Alireza; Mohan-Saïd, Sadek; Mueller, Michael; Muldrew, Alyson; Nunes, Sandrina; Oexle, Konrad; Rahi, Jugnoo; Raitakari, Olli; Ribeiro, Luisa; Rougier, Marie-Bénédicte; Sahel, José; Salonikiou, Aggeliki; Sanchez, Clarisa; Schmitz-Valckenberg, Steffen; Schweitzer, Cédric; Shehata, Jasmin; Silvestri, Giuliana; Simader, Christian; Souied, Eric; Springelkamp, Henriet; Tapp, Robyn; Verhoeven, Virginie; Von Hanno, Therese; Vujosevic, Stela; Williams, Katie; Wolfram, Christian; Yip, Jennifer; Zerbib, Jennyfer; Zwiener, Isabella

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  8. A class of degenerate stochastic differential equations with non ...

    Indian Academy of Sciences (India)

    We obtain sufficient condition for SDEs to evolve in the positive orthant. We use arguments based on comparison theorems for SDEs to achieve this. As an application we prove the existence of a unique strong solution for a class of multidimensional degenerate SDEs with non-Lipschitz diffusion coefficients.

  9. Referral Patterns for Syndromes Associated With Frontotemporal Lobar Degeneration

    OpenAIRE

    Chow, Tiffany W.; Hodges, John R.; Dawson, Kate E.; Miller, Bruce L.; Smith, Virginia; Mendez, Mario F.; Lipton, Anne M.

    2005-01-01

    We compared demographics of subjects diagnosed with frontotemporal degeneration (FTD) at a group of 5 clinics specializing in this non-Alzheimer dementia against those subjects diagnosed at standard Alzheimer disease centers, to determine any differences in referral patterns between such clinics.

  10. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

  11. A study of retrograde degeneration of median nerve forearm ...

    African Journals Online (AJOL)

    Mona Mokhtar El Bardawil

    2013-10-22

    Oct 22, 2013 ... A study of retrograde degeneration of median nerve forearm segment in carpal tunnel syndrome of variable severities. Mona Mokhtar El Bardawil, Gihan Abd El Latief Younis,. Marwa Mohammed Hassan, Eman Ramadan Mohammed *. Alexandria University, Department of Physical Medicine, ...

  12. A study of retrograde degeneration of median nerve forearm ...

    African Journals Online (AJOL)

    Introduction: Carpal tunnel syndrome (CTS) is a disorder of the hand which results from compression of the median nerve within its fibro-osseous tunnel at the wrist. The slowing in the forearm motor conduction velocity suggests the presence of retrograde degeneration. Existing studies conflict regarding a correlation ...

  13. Adjacent segment degeneration: observations in a goat spinal fusion study

    NARCIS (Netherlands)

    Hoogendoorn, R.J.W.; Helder, M.N.; Wuisman, P.I.J.M.; Bank, R.A.; Everts, V.; Smit, T.H.

    2008-01-01

    Study Design. The adjacent discs of 13 goats, originally used in a lumbar spinal fusion model study, were analyzed for symptoms of intervertebral disc degeneration by means of magnetic resonance imaging (MRI), macroscopy, and histology. These goats were followed for 6 months and the results were

  14. Adjacent segment degeneration: observations in a goat spinal fusion study

    NARCIS (Netherlands)

    Hoogendoorn, Roel J. W.; Helder, Macro N.; Wuisman, Paul I. J. M.; Bank, Ruud A.; Everts, Vincent E.; Smit, Theo H.

    2008-01-01

    The adjacent discs of 13 goats, originally used in a lumbar spinal fusion model study, were analyzed for symptoms of intervertebral disc degeneration by means of magnetic resonance imaging (MRI), macroscopy, and histology. These goats were followed for 6 months and the results were compared with 6

  15. Bovine explant model of degeneration of the intervertebral disc

    Directory of Open Access Journals (Sweden)

    Sivan Sarit

    2008-02-01

    Full Text Available Abstract Background Many new treatments for degeneration of the intervertebral disc are being developed which can be delivered through a needle. These require testing in model systems before being used in human patients. Unfortunately, because of differences in anatomy, there are no ideal animal models of disc degeneration. Bovine explant model systems have many advantages but it is not possible to inject any significant volume into an intact disc. Therefore we have attempted to mimic disc degeneration in an explant bovine model via enzymatic digestion. Methods Bovine coccygeal discs were incubated with different concentrations of the proteolytic enzymes, trypsin and papain, and maintained in culture for up to 3 weeks. A radio-opaque solution was injected to visualise cavities generated. Degenerative features were monitored histologically and biochemically (water and glycosaminoglycan content, via dimethylmethylene blue. Results and Conclusion The central region of both papain and trypsin treated discs was macro- and microscopically fragmented, with severe loss of metachromasia. The integrity of the surrounding tissue was mostly in tact with cells in the outer annulus appearing viable. Biochemical analysis demonstrated greatly reduced glycosaminoglycan content in these compared to untreated discs. We have shown that bovine coccygeal discs, treated with proteolytic enzymes can provide a useful in vitro model system for developing and testing potential new treatments of disc degeneration, such as injectable implants or biological therapies.

  16. Treatment of dry age-related macular degeneration with dobesilate

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

    2012-01-01

    The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

  17. Ion waves driven by shear flow in a relativistic degenerate ...

    Indian Academy of Sciences (India)

    2015-11-27

    Home; Journals; Pramana – Journal of Physics; Volume 86; Issue 5. Ion waves driven by shear flow in a relativistic degenerate ... Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015. Guest Editors: ...

  18. Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

    Directory of Open Access Journals (Sweden)

    Marco Mainardi

    2015-01-01

    Full Text Available Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression, structural plasticity (i.e., dynamics of dendritic spines, and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

  19. Spatial memory and hippocampal function: Where are we now?

    Directory of Open Access Journals (Sweden)

    Mark Good

    2002-01-01

    Full Text Available The main aim of this paper is to provide an overview of current debates concerning the role of the mammalian hippocampus in learning with a particular emphasis on spatial learning. The review discusses recent debates on (1 the role of the primate hippocampus in recognition memory and object-in-place memory, (2 the role of the hippocampus in spatial navigation in both rats and humans, and (3 the effects of hippocampal damage on processing contextual information. Evidence from these lines of research have led many current theories to posit a function for the hippocampus that has as its organizing principle the association or binding of stimulus representations. Based on this principle, recent theories of hippocampal function have extended their application beyond the spatial domain to capture features of declarative and episodic memory processes.

  20. The impact of sleep loss on hippocampal function

    Science.gov (United States)

    Prince, Toni-Moi; Abel, Ted

    2013-01-01

    Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-learning sleep deprivation on memory consolidation. Obtaining adequate sleep is challenging in a society that values “work around the clock.” Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is key. However, there are a limited number of therapeutics that are able to enhance cognition in the face of insufficient sleep. The identification of molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs. PMID:24045505