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https://www.readbyqxmd.com/read/29155785/modeling-neuronal-death-and-degeneration-in-mouse-primary-cerebellar-granule-neurons
#1
Matthew Laaper, Takrima Haque, Ruth S Slack, Arezu Jahani-Asl
Cerebellar granule neurons (CGNs) are a commonly used neuronal model, forming an abundant homogeneous population in the cerebellum. In light of their post-natal development, abundance, and accessibility, CGNs are an ideal model to study neuronal processes, including neuronal development, neuronal migration, and physiological neuronal activity stimulation. In addition, CGN cultures provide an excellent model for studying different modes of cell death including excitotoxicity and apoptosis. Within a week in culture, CGNs express N-methyl-D-aspartate (NMDA) receptors, a specific ionotropic glutamate receptor with many critical functions in neuronal health and disease...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155703/modeling-amyloid-%C3%AE-42-toxicity-and-neurodegeneration-in-adult-zebrafish-brain
#2
Prabesh Bhattarai, Alvin Kuriakose Thomas, Mehmet Ilyas Cosacak, Christos Papadimitriou, Violeta Mashkaryan, Yixin Zhang, Caghan Kizil
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons in the case of AD in part due to impaired proliferative capacity of the neural stem/progenitor cells (NSPCs) and reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance the proliferation and neurogenic capacity of NSPCs. Zebrafish (Danio rerio) is a regenerative organism, and we can learn the basic molecular programs with which we could design therapeutic approaches to tackle AD...
October 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#3
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29155051/peripheral-monocyte-entry-is-required-for-alpha-synuclein-induced-inflammation-and-neurodegeneration-in-a-model-of-parkinson-disease
#4
Ashley S Harms, Aaron D Thome, Zhaoqi Yan, Aubrey M Schonhoff, Gregory P Williams, Xinru Li, Yudong Liu, Hongwei Qin, Etty N Benveniste, David G Standaert
Accumulation of alpha-synuclein (α-syn) in the central nervous system (CNS) is a core feature of Parkinson disease (PD) that leads to activation of the innate immune system, production of inflammatory cytokines and chemokines, and subsequent neurodegeneration. Here, we used heterozygous reporter knock-in mice in which the first exons of the fractalkine receptor (CX3CR1) and of the C-C chemokine receptor type 2 (CCR2) are replaced with fluorescent reporters to study the role of resident microglia (CX3CR1+) and infiltrating peripheral monocytes (CCR2+), respectively, in the CNS...
November 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29153610/tdp-43-proteolysis-is-associated-with-astrocyte-reactivity-after-traumatic-brain-injury-in-rodents
#5
Chih-Yuan Huang, Yi-Che Lee, Ping-Chia Li, Po-Chou Liliang, Kang Lu, Kuo-Wei Wang, Li-Ching Chang, Li-Yen Shiu, Ming-Feng Chen, Yuan-Ting Sun, Hao-Kuang Wang
The aggregation and deposition of transactivation response DNA-binding protein 43 (TDP-43) in neurons and astrocytes is characteristic in a number of neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Nevertheless, the exact role of TDP-43 in astrocytes is unknown. Recently, TDP-43 was identified in neurons but not astrocytes after traumatic brain injury (TBI) in humans. In the present study, we evaluated TDP-43 expression and proteolysis in astrocytes in a rat model of TBI...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29153394/vcp-p97-mediated-unfolding-as-a-principle-in-protein-homeostasis-and-signaling
#6
REVIEW
Johannes van den Boom, Hemmo Meyer
The AAA+-type ATPase p97 governs an ever-expanding number of cellular processes reaching from degradation of damaged proteins and organelles to key signaling events and chromatin regulation with thousands of client proteins. With its relevance for cellular homeostasis and genome stability, it is linked to muscular and neuronal degeneration and, conversely, constitutes an attractive anti-cancer drug target. Its molecular function is ATP-driven protein unfolding, which is directed by ubiquitin and assisted by a host of cofactor proteins...
November 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29150945/development-of-an-in-vivo-mouse-model-of-discogenic-low-back-pain
#7
Changgui Shi, Vaskar Das, Xin Li, Ranjan Kc, Sujun Qiu, InSug O-Sullivan, Richard L Ripper, Jeffrey S Kroin, Fackson Mwale, Atiyayein A Wallace, Bingqian Zhu, Lan Zhao, Andre J van Wijnen, Mingliang Ji, Jun Lu, Gina Votta-Velis, Wen Yuan, Hee-Jeong Im
Discogenic Low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150919/a-focus-on-the-beneficial-effects-of-alpha-synuclein-and-a-re-appraisal-of-synucleinopathies
#8
Larisa Ryskalin, Carla L Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella, Francesco Fornai
Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owing an abnormal structure (as occurring following point gene mutations)...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29150520/dopaminergic-neurotoxins-induce-cell-death-by-attenuating-nf-%C3%AE%C2%BAb-mediated-regulation-of-trpc1-expression-and-autophagy
#9
Pramod Sukumaran, Yuyang Sun, Neil Antonson, Brij B Singh
Alterations in Ca(2+) homeostasis affect neuronal survival. However, the identity of Ca(2+) channels and the mechanisms underlying neurotoxin-induced neuronal degeneration are not well understood. In this study, the dopaminergic neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl -4-phenylpyridium ions (MPP(+)/MPTP), which mimic Parkinson's disease (PD), induced neuronal degeneration by decreasing store-mediated Ca(2+) entry. The function of the transient receptor potential canonical (TRPC)-1 channel was decreased upon exposure to the neurotoxins, followed by a decrease in TRPC1 expression...
November 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29149916/whole-exome-sequencing-in-amyotrophic-lateral-sclerosis-suggests-nek1-is-a-risk-gene-in-chinese
#10
Jacob Gratten, Qiongyi Zhao, Beben Benyamin, Fleur Garton, Ji He, Paul J Leo, Marie Mangelsdorf, Lisa Anderson, Zong-Hong Zhang, Lu Chen, Xiang-Ding Chen, Katie Cremin, Hong-Weng Deng, Janette Edson, Ying-Ying Han, Jessica Harris, Anjali K Henders, Zi-Bing Jin, Zhongshan Li, Yong Lin, Xiaolu Liu, Mhairi Marshall, Bryan J Mowry, Shu Ran, David C Reutens, Sharon Song, Li-Jun Tan, Lu Tang, Robyn H Wallace, Lawrie Wheeler, Jinyu Wu, Jian Yang, Huji Xu, Peter M Visscher, Perry F Bartlett, Matthew A Brown, Naomi R Wray, Dongsheng Fan
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry...
November 17, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29149899/selective-depletion-of-microglial-progranulin-in-mice-is-not-sufficient-to-cause-neuronal-ceroid-lipofuscinosis-or-neuroinflammation
#11
Terri L Petkau, Natalia Kosior, Kathleen de Asis, Colúm Connolly, Blair R Leavitt
BACKGROUND: Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice...
November 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#12
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29147910/therapeutic-activities-of-dj-1-and-its-binding-compounds-against-neurodegenerative-diseases
#13
Masatoshi Inden, Daijiro Yanagisawa, Masanori Hijioka, Hiroyoshi Ariga, Yoshihisa Kitamura
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Previously, we identified binding compounds of DJ-1, including UCP0045037/compound A, UCP0054278/compound B, and compound-23 (comp-23), by in silico virtual screening. These compounds prevented oxidative stress-induced dopaminergic neuronal death and restored locomotion defects in animal models of PD...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29146879/2-cl-mgv-1-ameliorates-apoptosis-in-the-thalamus-and-hippocampus-and-cognitive-deficits-after-cortical-infarct-in-rats
#14
Yicong Chen, Leo Veenman, Sukhdev Singh, Fubing Ouyang, Jiahui Liang, Weixian Huang, Ilan Marek, Jinsheng Zeng, Moshe Gavish
BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl)quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction...
November 16, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29143476/differences-in-innervated-neurons-of-the-internal-anal-sphincter-based-on-age-and-sex-a-histological-study
#15
Tomoaki Kaneko, Tetsuo Nemoto, Kimihiko Funahashi, Junichi Koike, Kazutoshi Shibuya, Hironori Kaneko
AIM: Previous studies have shown sex and age differences in anal sphincter function, but few morphological studies have focused on the quality and quantity of the nerves that control the sphincter muscles. The present study aimed to determine whether there are morphological and quantitative sex and age differences in the nerves in the conjoined longitudinal muscle. METHODS: This was a single-center, retrospective study using surgical specimens from 44 patients who underwent abdominoperineal resection between 2003 and 2012...
November 15, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/29142739/classification-of-amyotrophic-lateral-sclerosis-disease-based-on-convolutional-neural-network-and-reinforcement-sample-learning-algorithm
#16
Abdulkadir Sengur, Yaman Akbulut, Yanhui Guo, Varun Bajaj
Electromyogram (EMG) signals contain useful information of the neuromuscular diseases like amyotrophic lateral sclerosis (ALS). ALS is a well-known brain disease, which can progressively degenerate the motor neurons. In this paper, we propose a deep learning based method for efficient classification of ALS and normal EMG signals. Spectrogram, continuous wavelet transform (CWT), and smoothed pseudo Wigner-Ville distribution (SPWVD) have been employed for time-frequency (T-F) representation of EMG signals. A convolutional neural network is employed to classify these features...
December 2017: Health Information Science and Systems
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#17
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142100/abnormal-visual-gain-control-and-excitotoxicity-in-early-onset-parkinson-s-disease-drosophila-models
#18
Marc Mason Himmelberg, Ryan J H West, Christopher J H Elliott, Alex R Wade
The excitotoxic theory of Parkinson's disease (PD) hypothesises that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD Drosophila models DJ-1Δ72, DJ1-Δ93, and PINK15. We used an electroretinogram to record steady state visually evoked potentials driven by temporal contrast stimuli...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29140847/overexpressed-wild-type-superoxide-dismutase-1-exhibits-amyotrophic-lateral-sclerosis-related-misfolded-conformation-in-induced-pluripotent-stem-cell-derived-spinal-motor-neurons
#19
Kenichi Komatsu, Keiko Imamura, Hirofumi Yamashita, Jean-Pierre Julien, Ryosuke Takahashi, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which motor neurons selectively degenerate. Superoxide dismutase 1 (SOD1) was found to be a causative gene of familial ALS, and mutant SOD1 transgenic mice recapitulated ALS phenotypes. Analysis of these mice showed accumulation of misfolded SOD1 protein in motor neurons. Misfolded SOD1 accumulation was found in spinal motor neurons of both familial ALS patients with the SOD1 mutation and sporadic ALS patients. However, it is unclear what condition causes wild-type SOD1 misfolding in patients without the SOD1 mutation...
November 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/29138458/low-intensity-pulsed-ultrasound-improves-behavioral-and-histological-outcomes-after-experimental-traumatic-brain-injury
#20
Wei-Shen Su, Chun-Hu Wu, Szu-Fu Chen, Feng-Yi Yang
The purpose of this study was to investigate the neuroprotective effects of low-intensity pulsed ultrasound (LIPUS) on behavioral and histological outcomes in a mouse model of traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury were treated with LIPUS in the injured region daily for a period of 4 weeks. The effects of LIPUS on edema were observed by MR imaging in the mouse brain at 1 and 4 days following TBI. Brain water content, blood-brain barrier permeability, histology analysis, and behavioral studies were performed to assess the effects of LIPUS...
November 14, 2017: Scientific Reports
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