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Molecular Brain

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https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#1
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28716096/optimizing-reproducibility-of-operant-testing-through-reinforcer-standardization-identification-of-key-nutritional-constituents-determining-reward-strength-in-touchscreens
#2
Eun Woo Kim, Benjamin U Phillips, Christopher J Heath, So Yeon Cho, Hyunjeong Kim, Jemeen Sreedharan, Ho-Taek Song, Jong Eun Lee, Timothy J Bussey, Chul Hoon Kim, Eosu Kim, Lisa M Saksida
Reliable and reproducible assessment of animal learning and behavior is a central aim of basic and translational neuroscience research. Recent developments in automated operant chamber technology have led to the possibility of universal standard protocols, in addition to increased translational potential, reliability and accuracy. However, the impact of regional and national differences in the supplies of available reinforcers in this system on behavioural performance and inter-laboratory variability is an unknown and at present uncontrolled variable...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28716058/srf-modulates-seizure-occurrence-activity-induced-gene-transcription-and-hippocampal-circuit-reorganization-in-the-mouse-pilocarpine-epilepsy-model
#3
Pascal Lösing, Cristina Elena Niturad, Merle Harrer, Christopher Meyer Zu Reckendorf, Theresa Schatz, Daniela Sinske, Holger Lerche, Snezana Maljevic, Bernd Knöll
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28683812/mechano-growth-factor-a-splice-variant-of-igf-1-promotes-neurogenesis-in-the-aging-mouse-brain
#4
Jason J Tang, Jewel L Podratz, Miranda Lange, Heidi J Scrable, Mi-Hyeon Jang, Anthony J Windebank
Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG)...
July 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28673309/abnormal-circadian-oscillation-of-hippocampal-mapk-activity-and-power-spectrums-in-nf1-mutant-mice
#5
Lei Chen, Tatiana Serdyuk, Beimeng Yang, Shuai Wang, Shiqing Chen, Xixia Chu, Xu Zhang, Jinjing Song, Hechen Bao, Chengbin Zhou, Xiang Wang, Shuangle Dong, Lulu Song, Fujun Chen, Guang He, Lin He, Ying Zhou, Weidong Li
Studies have implied that the circadian oscillation of mitogen-activated protein kinase (MAPK) signal pathways is crucial for hippocampus-dependent memory. NF1 mouse models (Nf1 heterozygous null mutants; Nf1 (+/-)) displayed enhanced MAPK activity in the hippocampus and resulted in memory deficits. We assumed a link between MAPK pathways and hippocampal rhythmic oscillations, which have never been explored in Nf1 (+/-) mice. We demonstrated that the level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in Nf1 (+/-) mice were significantly higher at nighttime than at daytime...
July 3, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28646910/the-role-of-5-ht-receptors-in-depression
#6
REVIEW
Christine N Yohn, Mark M Gergues, Benjamin Adam Samuels
Depression is a polygenic and highly complex psychiatric disorder that remains a major burden on society. Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are some of the most commonly prescribed drugs worldwide. In this review, we will discuss the evidence that links serotonin and serotonin receptors to the etiology of depression and the mechanisms underlying response to antidepressant treatment. We will then revisit the role of serotonin in three distinct hypotheses that have been proposed over the last several decades to explain the pathophysiology of depression: the monoamine, neurotrophic, and neurogenic hypotheses...
June 24, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28646881/heme-molecule-functions-as-an-endogenous-agonist-of-astrocyte-tlr2-to-contribute-to-secondary-brain-damage-after-intracerebral-hemorrhage
#7
Hyunjung Min, Boomin Choi, Yong Ho Jang, Ik-Hyun Cho, Sung Joong Lee
Toll-like receptor 2 (TLR2) was recently shown to contribute to secondary brain damage after intracerebral hemorrhage (ICH), although the molecular mechanisms of this contribution are elusive. In this study, we tested the hypothesis that hemin functions as a TLR2 endogenous agonist, causing proinflammatory astrocyte activation and secondary brain damage after ICH. Hemin administration to the mouse brain striatum induced ICH injury and neurological deficits, however, the brain injury volume and neurological deficits due to hemin injection were significantly reduced in TLR2 knock-out (KO) mice...
June 24, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28637489/synaptoimmunology-roles-in-health-and-disease
#8
REVIEW
Robert Nisticò, Eric Salter, Celine Nicolas, Marco Feligioni, Dalila Mango, Zuner A Bortolotto, Pierre Gressens, Graham L Collingridge, Stephane Peineau
Mounting evidence suggests that the nervous and immune systems are intricately linked. Many proteins first identified in the immune system have since been detected at synapses, playing different roles in normal and pathological situations. In addition, novel immunological functions are emerging for proteins typically expressed at synapses. Under normal conditions, release of inflammatory mediators generally represents an adaptive and regulated response of the brain to immune signals. On the other hand, when immune challenge becomes prolonged and/or uncontrolled, the consequent inflammatory response leads to maladaptive synaptic plasticity and brain disorders...
June 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#9
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28623920/ketamine-induced-apoptosis-in-the-mouse-cerebral-cortex-follows-similar-characteristic-of-physiological-apoptosis-and-can-be-regulated-by-neuronal-activity
#10
Qi Wang, Feng-Yan Shen, Rong Zou, Jing-Jing Zheng, Xiang Yu, Ying-Wei Wang
The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry...
June 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28610619/amyotrophic-lateral-sclerosis-patient-ipsc-derived-astrocytes-impair-autophagy-via-non-cell-autonomous-mechanisms
#11
Martin Madill, Katya McDonagh, Jun Ma, Alice Vajda, Paul McLoughlin, Timothy O'Brien, Orla Hardiman, Sanbing Shen
Amyotrophic lateral sclerosis, a devastating neurodegenerative disease, is characterized by the progressive loss of motor neurons and the accumulation of misfolded protein aggregates. The latter suggests impaired proteostasis may be a key factor in disease pathogenesis, though the underlying mechanisms leading to the accumulation of aggregates is unclear. Further, recent studies have indicated that motor neuron cell death may be mediated by astrocytes. Herein we demonstrate that ALS patient iPSC-derived astrocytes modulate the autophagy pathway in a non-cell autonomous manner...
June 13, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28606116/characterization-of-serotonin-induced-inhibition-of-excitatory-synaptic-transmission-in-the-anterior-cingulate-cortex
#12
Zhen Tian, Manabu Yamanaka, Matteo Bernabucci, Ming-Gao Zhao, Min Zhuo
Excitatory synaptic transmission in central synapses is modulated by serotonin (5-HT). The anterior cingulate cortex (ACC) is an important cortical region for pain perception and emotion. ACC neurons receive innervation of projecting serotonergic nerve terminals from raphe nuclei, but the possible effect of 5-HT on excitatory transmission in the ACC has not been investigated. In the present study, we investigated the role of 5-HT on glutamate neurotransmission in the ACC slices of adult mice. Bath application of 5-HT produced dose-dependent inhibition of evoked excitatory postsynaptic currents (eEPSCs)...
June 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28592261/trem2-protects-against-cerebral-ischemia-reperfusion-injury
#13
Rong Wu, Xiangpen Li, Pengfei Xu, Likui Huang, Jinping Cheng, Xiaolong Huang, Jingru Jiang, Long-Jun Wu, Yamei Tang
Although post-ischemic inflammation induced by the innate immune response is considered an essential step in the progression of cerebral ischemia injury, the role of triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of ischemic stroke remains to be elucidated. Here, we found that the transcriptional and post-transcriptional levels of TREM2 were increased in cultured primary microglia after oxygen-glucose deprivation and reoxygenation and in the ischemic penumbra of the cerebral cortex after middle cerebral artery occlusion (MCAO) and reperfusion in mice...
June 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28569173/apoe-isoforms-differentially-regulates-cleavage-and-secretion-of-bdnf
#14
Abhik Sen, Thomas J Nelson, Daniel L Alkon
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for sporadic or late onset Alzheimer's disease (AD). Brain-derived neurotrophic factor (BDNF) is decreased by 3 to 4-fold in the brains of AD patients at autopsy. ApoE4 mice also have reduced BDNF levels. However, there have been no reports relating the different ApoE isoforms or AD to differential regulation of BDNF. Here we report that in the hippocampal regions of AD patients both prepro-BDNF and pro-BDNF expression showed a 40 and 60% decrease respectively compared to that expression in the hippocampi of age-matched control patients...
June 1, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28558799/propagation-of-tau-aggregates
#15
REVIEW
Michel Goedert, Maria Grazia Spillantini
Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells...
May 30, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28535795/turtle-interacts-with-borderless-in-regulating-glial-extension-and-axon-ensheathment
#16
Yixu Chen, Scott Cameron, Wen-Tzu Chang, Yong Rao
Proper recognition between axons and glial processes is required for the establishment of axon ensheathment in the developing nervous system. Recent studies have begun to reveal molecular events underlying developmental control of axon-glia recognition. In our previous work, we showed that the transmembrane protein Borderless (Bdl) is specifically expressed in wrapping glia (WG), and is required for the extension of glial processes and the ensheathment of photoreceptor axons in the developing Drosophila visual system...
May 23, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28521778/cortical-kainate-receptors-and-behavioral-anxiety
#17
REVIEW
Min Zhuo
The study of glutamatergic synapses mainly focuses on the memory-related hippocampus. Recent studies in the cortical areas such as the anterior cingulate cortex (ACC) show that excitatory synapses can undergo long-term plastic changes in adult animals. Long-term potentiation (LTP) of cortical synapses may play important roles in chronic pain and anxiety. In addition to NMDA and AMPA receptors, kainate (KA) receptors have been found to play roles in synaptic transmission, regulation and presynaptic forms of LTP...
May 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28446243/targeting-metabotropic-glutamate-receptors-for-novel-treatments-of-schizophrenia
#18
REVIEW
James Maksymetz, Sean P Moran, P Jeffrey Conn
Support for the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia has led to increasing focus on restoring proper glutamatergic signaling as an approach for treatment of this devastating disease. The ability of metabotropic glutamate (mGlu) receptors to modulate glutamatergic neurotransmission has thus attracted considerable attention for the development of novel antipsychotics. Consisting of eight subtypes classified into three groups based on sequence homology, signal transduction, and pharmacology, the mGlu receptors provide a wide range of targets to modulate NMDAR function as well as glutamate release...
April 26, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28427452/modeling-environmental-risk-factors-of-autism-in-mice-induces-ibd-related-gut-microbial-dysbiosis-and-hyperserotonemia
#19
Joon Seo Lim, Mi Young Lim, Yongbin Choi, GwangPyo Ko
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD...
April 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28407788/absence-of-neurological-abnormalities-in-mice-homozygous-for-the-polr3a-g672e-hypomyelinating-leukodystrophy-mutation
#20
Karine Choquet, Sharon Yang, Robyn D Moir, Diane Forget, Roxanne Larivière, Annie Bouchard, Christian Poitras, Nicolas Sgarioto, Marie-Josée Dicaire, Forough Noohi, Timothy E Kennedy, Joseph Rochford, Geneviève Bernard, Martin Teichmann, Benoit Coulombe, Ian M Willis, Claudia L Kleinman, Bernard Brais
Recessive mutations in the ubiquitously expressed POLR3A gene cause one of the most frequent forms of childhood-onset hypomyelinating leukodystrophy (HLD): POLR3-HLD. POLR3A encodes the largest subunit of RNA Polymerase III (Pol III), which is responsible for the transcription of transfer RNAs (tRNAs) and a large array of other small non-coding RNAs. In order to study the central nervous system pathophysiology of the disease, we introduced the French Canadian founder Polr3a mutation c.2015G > A (p.G672E) in mice, generating homozygous knock-in (KI/KI) as well as compound heterozygous mice for one Polr3a KI and one null allele (KI/KO)...
April 13, 2017: Molecular Brain
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