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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/30611881/sirna-mediated-knockdown-of-b3galt4-decreases-gm1-ganglioside-expression-and-enhances-vulnerability-for-neurodegeneration
#1
Megha Verma, Jay S Schneider
Reduced levels of brain gangliosides GD1a, GD1b, GT1b and to a lesser extent GM1 have been found in substantia nigra (SN) from Parkinson's disease (PD) patients, along with decreased gene expression for key enzymes (B3Galt4, St3gal2) involved in synthesis of these gangliosides. Based on these observations, the present study examined the extent to which decreased expression of B3GALT4 mRNA and resulting decreased levels of GM1 ganglioside in dopaminergic cells may increase the vulnerability of these cells to degeneration in response to a neurotoxicant exposure that under normal circumstances would not result in neurodegeneration...
January 3, 2019: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30610998/alteration-of-parvalbumin-expression-and-perineuronal-nets-formation-in-the-cerebral-cortex-of-aged-mice
#2
Hiroshi Ueno, Kazuki Fujii, Keizo Takao, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara
Aging is associated with decline in cognitive function, but the underlying mechanisms have not been elucidated. Normal activity of pyramidal cells and parvalbumin-expressing interneurons (PV neurons) is essential for cognitive function. PV neurons participate in the regulation of pyramidal-cell firing. Abnormal function of PV neurons may occur with aging. We analyzed the density and the percentage of PV neurons surrounded by perineuronal nets (PNNs) in the entire cortex of adult (3-month-old) and aged (24-month-old) mice...
January 2, 2019: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30594669/ouabain-activates-transcription-factor-eb-and-exerts-neuroprotection-in-models-of-alzheimer-s-disease
#3
Ha-Lim Song, Atanas Vladimirov Demirev, Na-Young Kim, Dong-Hou Kim, Seung-Yong Yoon
The number of neurofibrillary tangles containing abnormal hyperphosphorylated tau protein correlates with the degree of dementia in Alzheimer's disease (AD). In addition, autophagosome accumulation and disturbance of autophagy, the process by which toxic aggregate proteins are degraded in the cytosol, are also found in AD models. These indicate that regulation of the autophagy-lysosome system may be a potential therapeutic target for AD. Activation of transcription factor EB (TFEB), a master regulator of autophagy-lysosome system gene transcription, reduces the amount of tau in APP mice...
December 27, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30562574/impairment-of-chaperone-mediated-autophagy-affects-neuronal-homeostasis-through-altered-expression-of-dj-1-and-crmp-2-proteins
#4
Oeystein Roed Brekk, Manousos Makridakis, Panagiota Mavroeidi, Antonia Vlahou, Maria Xilouri, Leonidas Stefanis
Chaperone-mediated autophagy (CMA) is a substrate-specific mode of lysosomal proteolysis, with multiple lines of evidence connecting its dysfunction to both ageing and disease. We have recently shown that CMA impairment through knock-down of the lysosomal receptor LAMP2A is detrimental to neuronal viability in vivo; however, it is not clear which subset of proteins regulated by the CMA pathway mediate such changes. In this study, we have manipulated CMA function through alterations of LAMP2A abundance of utilizing primary rat cortical neurons, to identify potential changes to the neuronal proteome occurring prior to actual toxic effects...
December 15, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30543858/cerebrospinal-fluid-biomarker-for-parkinson-s-disease-an-overview
#5
REVIEW
Fabian Maass, Isabel Schulz, Paul Lingor, Brit Mollenhauer, Mathias Bähr
In Parkinson's disease (PD), there is a wide field of recent and ongoing search for useful biomarkers for early and differential diagnosis, disease monitoring or subtype characterization. Up to now, no biofluid biomarker has entered the daily clinical routine. Cerebrospinal fluid (CSF) is often used as a source for biomarker development in different neurological disorders because it reflects changes in central-nervous system homeostasis. This review article gives an overview about different biomarker approaches in PD, mainly focusing on CSF analyses...
December 10, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30537535/fluid-and-pet-biomarkers-for-amyloid-pathology-in-alzheimer-s-disease
#6
REVIEW
Ann D Cohen, Susan M Landau, Beth E Snitz, William E Klunk, Kaj Blennow, Henrik Zetterberg
Alzheimer's disease (AD) is characterized by amyloid plaques and tau pathology (neurofibrillary tangles and neuropil threads). Amyloid plaques are primarily composed of aggregated and oligomeric β-amyloid (Aβ) peptides ending at position 42 (Aβ42). The development of fluid and PET biomarkers for Alzheimer's disease (AD), has allowed for detection of Aβ pathology in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer's disease (AD). In the recent National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework, AD is defined by the underlying pathology as measured in patients during life by biomarkers (Jack et al...
December 8, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30529601/biomarkers-for-tau-pathology
#7
REVIEW
Michael Schöll, Anne Maass, Niklas Mattsson, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, William Jagust
The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions...
December 6, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30529228/melanocortin-4-receptor-activation-protects-striatal-neurons-and-glial-cells-from-3-nitropropionic-acid-toxicity
#8
Julieta Saba, Lila Carniglia, Delia Ramírez, Juan Turati, Mercedes Imsen, Daniela Durand, Mercedes Lasaga, Carla Caruso
α-Melanocyte stimulating hormone (α-MSH) is a melanocortin which exerts potent anti-inflammatory and anti-apoptotic effects. Melanocortin 4 receptors (MC4R) are abundantly expressed in the brain and we previously demonstrated that [Nle(4), D-Phe(7)]melanocyte-stimulating hormone (NDP-MSH), an α-MSH analogue, increased expression of brain derived-neurotrophic factor (BDNF), and peroxisome proliferator-activated receptor-γ (PPAR-γ). We hypothesized that melanocortins could affect striatal cell survival through BDNF and PPAR-γ...
December 4, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30529227/review-fluid-biomarkers-in-the-human-prion-diseases
#9
REVIEW
Andrew G B Thompson, Simon H Mead
The human prion diseases are a diverse set of often rapidly progressive neurodegenerative conditions associated with abnormal forms of the prion protein. We review work to establish diagnostic biomarkers and assays that might fill other important roles, particularly those that could assist the planning and interpretation of clinical trials. The field now benefits from highly sensitive and specific diagnostic biomarkers using cerebrospinal fluid: detecting by-products of rapid neurodegeneration or specific functional properties of abnormal prion protein, with the second generation real time quaking induced conversion (RT-QuIC) assay being particularly promising...
December 4, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30439413/cyclo-his-pro-inhibits-nlrp3-inflammasome-cascade-in-als-microglial-cells
#10
Silvia Grottelli, Letizia Mezzasoma, Paolo Scarpelli, Ivana Cacciatore, Barbara Cellini, Ilaria Bellezza
Neuroinflammation, i.e. self-propelling progressive cycle of microglial activation and neuron damage, as well as improper protein folding, are recognized as major culprits of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Mutations in several proteins have been linked to ALS pathogenesis, including the G93A mutation in the superoxide dismutase 1 (SOD1) enzyme. SOD1(G93A) mutant is prone to aggregate thus inducing both oxidative stress and neuroinflammation. In this study we used hSOD1(G93A) microglial cells to investigate the effects of the antioxidant and anti-inflammatory cyclic dipeptide (His-Pro) on LPS-induced inflammasome activation...
November 13, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30408526/interaction-of-nectin-2%C3%AE-with-the-auxiliary-protein-of-the-voltage-gated-a-type-k-channel-kv4-2-dipeptidyl-aminopeptidase-like-protein-at-the-boundary-between-the-adjacent-somata-of-clustered-cholinergic-neurons-in-the-medial-habenula
#11
Hajime Shiotani, Muneaki Miyata, Kiyohito Mizutani, Shujie Wang, Akira Mizoguchi, Hideki Mochizuki, Kenji Mandai, Yoshimi Takai
The medial habenula (MHb) receives septal inputs and sends efferents to the interpeduncular nucleus and is implicated in stress, depression, memory, and nicotine withdrawal syndrome. We previously showed by immunofluorescence microscopy that the cell adhesion molecule nectin-2α is expressed in the cholinergic neurons in the developing and adult mouse MHbs and localized at the boundary between the adjacent somata of clustered cholinergic neurons where the voltage-gated A-type K+ channel Kv4.2 is localized. We further showed by immunoelectron microscopy that Kv4...
November 5, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30404024/strain-differences-in-hippocampal-synaptic-dysfunction-in-the-tgcrnd8-mouse-model-of-alzheimer-s-disease-implications-for-improving-translational-capacity
#12
Wanda M Snow, Kensuke Oikawa, Jelena Djordjevic, Benedict C Albensi
In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid β plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mice in this model, but whether this extends to synaptic function is unknown. We investigated the influence of background strain on basal synaptic transmission and long-term potentiation (LTP) in the hippocampus of TgCRND8 mice (13-16 months) on hybrid backgrounds of (129SvEv/Tac) x (C3H/C57/129SvEv/Tac) (aka "129") or (C57) x (C3H/C57) (aka "C3H")...
November 4, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30399416/biomarkers-for-diseases-with-tdp-43-pathology
#13
REVIEW
Petra Steinacker, Peggy Barschke, Markus Otto
The discovery that aggregated transactive response DNA-binding protein 43 kDa (TDP-43) is the major component of pathological ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) caused seminal progress in the unveiling of the genetic bases and molecular characteristics of these now so-called TDP-43 proteinopathies. Substantial increase in the knowledge of clinic-pathological coherencies, especially for FTLD variants, could be made in the last decade, but also revealed a considerable complexity of TDP-43 pathology and often a poor correlation of clinical and molecular disease characteristics...
November 3, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30391355/a-new-function-for-prokineticin-2-recruitment-of-svz-derived-neuroblasts-to-the-injured-cortex-in-a-mouse-model-of-traumatic-brain-injury
#14
Mayara Vieira Mundim, Laura Nicoleti Zamproni, Agnes Araújo Sardinha Pinto, Layla Testa Galindo, André Machado Xavier, Isaias Glezer, Marimélia Porcionatto
Traumatic brain injury is an important cause of global morbidity and mortality. After an initial injury, there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim to both counteract these mechanisms and replenish the lost cell population in order to improve recovery. The adult mammal brain has at least two neurogenic regions that maintain physiological functions: the subgranular zone of the dentate gyrus in the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) adjacent to the lateral ventricles, which produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs...
November 1, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30253196/centella-asiatica-attenuates-hippocampal-mitochondrial-dysfunction-and-improves-memory-and-executive-function-in-%C3%AE-amyloid-overexpressing-mice
#15
Nora E Gray, Jonathan A Zweig, Maya Caruso, Jennifer Y Zhu, Kirsten M Wright, Joseph F Quinn, Amala Soumyanath
Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its in vivo mechanism of improving Aβ-related cognitive impairment. This study investigates the effects of CAW on learning, memory and executive function as well as mitochondrial function and antioxidant response in the 5xFAD model of Aβ accumulation...
December 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30342995/d-cysteine-promotes-dendritic-development-in-primary-cultured-cerebellar-purkinje-cells-via-hydrogen-sulfide-production
#16
Takahiro Seki, Masahiro Sato, Ayumu Konno, Hirokazu Hirai, Yuki Kurauchi, Akinori Hisatsune, Hiroshi Katsuki
Hydrogen sulfide and reactive sulfur species are regulators of physiological functions, have antioxidant effects against oxidative stresses, and are endogenously generated from l-cysteine. Recently, a novel pathway that generates hydrogen sulfide and reactive sulfur species from d-cysteine has been identified. d-Amino acid oxidase (DAO) is involved in this pathway and, among the various brain regions, is especially abundant in the cerebellum. d-Cysteine has been found to be a better substrate in the generation of hydrogen sulfide in the cerebellum than l-cysteine...
October 19, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30315869/validation-of-reference-genes-for-normalization-of-real-time-quantitative-pcr-studies-of-gene-expression-in-brain-capillary-endothelial-cells-cultured-in-vitro
#17
Maria Hersom, Charlotte Goldeman, Natasia Pretzer, Birger Brodin
BACKGROUND: The genes encoding β-actin and GAPDH are two of the most commonly used reference genes for normalization in in vitro blood-brain barrier studies. Studies have, however, shown that these reference genes might not always be the best choice. The aim of the present study was to evaluate 10 reference genes for use in mRNA profiling studies in primary cultures of brain endothelial cells of bovine origin. METHODS: Gene evaluations were performed by qPCR in mono-culture and in co-cultures with astrocytes...
October 10, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30193933/effects-of-gem-dihydroperoxides-against-mutant-copper%C3%A2-zinc-superoxide-dismutase-mediated-neurotoxicity
#18
Tomoyuki Ueda, Masatoshi Inden, Yuta Asaka, Yuji Masaki, Hisaka Kurita, Wakako Tanaka, Eiji Yamaguchi, Akichika Itoh, Isao Hozumi
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathology is well investigated, currently, effective treatments are unavailable. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, including mutant copper‑zinc superoxide dismutase (SOD1), TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous reports have shown that excessive oxidative stress, associated with mitochondrial dysfunction and mutant protein accumulation, contributes to ALS pathology...
October 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30171894/deletion-of-kir6-2-sur1-potassium-channels-rescues-diminishing-of-da-neurons-via-decreasing-iron-accumulation-in-pd
#19
Qian Zhang, Chengwu Li, Ting Zhang, Yaping Ge, Xiaojuan Han, Sifan Sun, Jianhua Ding, Ming Lu, Gang Hu
ATP-sensitive potassium (K-ATP) channels express in the central nervous system extensively which coupling cell metabolism and cellular electrical activity. K-ATP channels in mature substantia nigra (SN) dopaminergic (DA) neurons are composed of inwardly rectifying potassium channel (Kir) subunit 6.2 and sulfonylurea receptor 1 (SUR1). Our previous study revealed that regulating K-ATP channel exerts the protective effect on DA neurons in a mouse model of Parkinson's disease (PD). However, the detailed mechanism underlying the role of Kir6...
October 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/30144504/neural-progenitors-derived-from-tuberous-sclerosis-complex-patients-exhibit-attenuated-pi3k-akt-signaling-and-delayed-neuronal-differentiation
#20
Avery J Zucco, Valentina Dal Pozzo, Alina Afinogenova, Ronald P Hart, Orrin Devinsky, Gabriella D'Arcangelo
Tuberous Sclerosis Complex (TSC) is a disease caused by autosomal dominant mutations in the TSC1 or TSC2 genes, and is characterized by tumor susceptibility, brain lesions, seizures and behavioral impairments. The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. TSC1/2 loss of heterozygosity (LOH) and the subsequent complete loss of TSC regulatory activity in null cells causes mTORC1 dysregulation and TSC-associated brain lesions or other tissue tumors...
October 2018: Molecular and Cellular Neurosciences
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