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Molecular Brain

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https://www.readbyqxmd.com/read/29925434/rnaseq-analysis-of-hippocampal-microglia-after-kainic-acid-induced-seizures
#1
Dale B Bosco, Jiaying Zheng, Zhiyan Xu, Jiyun Peng, Ukpong B Eyo, Ke Tang, Cheng Yan, Jun Huang, Lijie Feng, Gongxiong Wu, Jason R Richardson, Hui Wang, Long-Jun Wu
Microglia have been shown to be of critical importance to the progression of temporal lobe epilepsy. However, the broad transcriptional changes that these cells undergo following seizure induction is not well understood. As such, we utilized RNAseq analysis upon microglia isolated from the hippocampus to determine expression pattern alterations following kainic acid induced seizure. We determined that microglia undergo dramatic changes to their expression patterns, particularly with regard to mitochondrial activity and metabolism...
June 20, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29880005/nodding-behavior-couples-to-vigilance-fluctuation-in-a-high-calorie-diet-model-of-drowsiness
#2
Anna Shin, Jeonghoon Woo, Jung Eun Kim, Daesoo Kim
Drowsiness is an awake state with increased sleep drive, yet the neural correlates and underlying mechanisms remains unclear. Here, we established a mouse model of drowsiness, where mice are fasted for 1 day and then allowed to overeat high-fat food (to promote sleep) while positioned in an open-field box (to promote vigilance). They fall into a long-lasting drowsy state, as reflected by repeated and open-eyed nodding of the head while in a standing position. Simultaneous recording of electroencephalogram (EEG) and neck electromyogram (EMG) readouts revealed that this drowsy state including nodding state had multiple stages in terms of the relationship between the level of vigilance and head movement: delta oscillations decreased in power prior to the head-nodding period and increased during the non-nodding period...
June 7, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29866136/excitation-wavelength-optimization-improves-photostability-of-asap-family-gevis
#3
Fang Xu, Dong-Qing Shi, Pak-Ming Lau, Michael Z Lin, Guo-Qiang Bi
Recent interest in high-throughput recording of neuronal activity has motivated rapid improvements in genetically encoded calcium or voltage indicators (GECIs or GEVIs) for all-optical electrophysiology. Among these probes, the ASAPs, a series of voltage indicators based on a variant of circularly permuted green fluorescent protein (cpGFP) and a conjugated voltage sensitive domain (VSD), are capable of detecting both action potentials and subthreshold neuronal activities. Here we show that the ASAPs, when excited by blue light, undergo reversible photobleaching...
June 4, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29859117/gabaergic-deficits-and-schizophrenia-like-behaviors-in-a-mouse-model-carrying-patient-derived-neuroligin-2-r215h-mutation
#4
Dong-Yun Jiang, Zheng Wu, Cody Tieu Forsyth, Yi Hu, Siu-Pok Yee, Gong Chen
Schizophrenia (SCZ) is a severe mental disorder characterized by delusion, hallucination, and cognitive deficits. We have previously identified from schizophrenia patients a loss-of-function mutation Arg215 →His215 (R215H) of neuroligin 2 (NLGN2) gene, which encodes a cell adhesion molecule critical for GABAergic synapse formation and function. Here, we generated a novel transgenic mouse line with neuroligin-2 (NL2) R215H mutation. The single point mutation caused a significant loss of NL2 protein in vivo, reduced GABAergic transmission, and impaired hippocampal activation...
June 1, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29843805/systemic-overexpression-of-sqstm1-p62-accelerates-disease-onset-in-a-sod1-h46r-expressing-als-mouse-model
#5
Shun Mitsui, Asako Otomo, Masahisa Nozaki, Suzuka Ono, Kai Sato, Ryohei Shirakawa, Hiroaki Adachi, Masashi Aoki, Gen Sobue, Hui-Fang Shang, Shinji Hadano
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective loss of upper and lower motor neurons. Recent studies have shown that mutations in SQSTM1 are linked to ALS. SQSTM1 encodes SQSTM1/p62 that regulates not only autophagy via the association with MAP1LC3/LC3 and ubiquitinated proteins but also the KEAP1-NFE2L2/Nrf2 anti-oxidative stress pathway by interacting with KEAP1. Previously, we have demonstrated that loss of SQSTM1 exacerbates disease phenotypes in a SOD1H46R -expressing ALS mouse model...
May 29, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29801501/a-novel-extended-form-of-alpha-synuclein-3-utr-in-the-human-brain
#6
Goun Je, Subhrangshu Guhathakurta, Seung Pil Yun, Han Seok Ko, Yoon-Seong Kim
Alpha-synuclein (α-SYN) is one of the key contributors in Parkinson's disease (PD) pathogenesis. Despite the fact that increased α-SYN levels are considered one of the key contributors in developing PD, the molecular mechanisms underlying the regulation of α-SYN still needs to be elucidated. Since the 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) have important roles in translation, localization, and stability of mRNAs through RNA binding proteins (RBPs) and microRNAs (miRNAs), it is important to identify the exact length of 3'UTRs of transcripts in order to understand the precise regulation of gene expression...
May 25, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29793524/a-central-acting-connexin-inhibitor-ini-0602-prevents-high-fat-diet-induced-feeding-pattern-disturbances-and-obesity-in-mice
#7
Tsutomu Sasaki, Rika Numano, Hiromi Yokota-Hashimoto, Sho Matsui, Naobumi Kimura, Hideyuki Takeuchi, Tadahiro Kitamura
A high-fat diet (HFD) causes obesity by promoting excessive energy intake, and simultaneously, by disturbing the timing of energy intake. Restoring the feeding pattern is sufficient to prevent HFD-induced obesity in mice. However, the molecular mechanism(s) underlying HFD-induced feeding pattern disturbances remain elusive. Saturated fatty acids activate microglia and cause hypothalamic inflammation. Activated microglia cause neuroinflammation, which spreads via inflammatory cytokines and gap-junction hemichannels...
May 24, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29747665/comprehensive-behavioral-analysis-of-mice-deficient-in-rapgef2-and-rapgef6-a-subfamily-of-guanine-nucleotide-exchange-factors-for-rap-small-gtpases-possessing-the-ras-rap-associating-domain
#8
Kazuhiro Maeta, Satoko Hattori, Junji Ikutomo, Hironori Edamatsu, Shymaa E Bilasy, Tsuyoshi Miyakawa, Tohru Kataoka
Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology...
May 10, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29739425/naked-mole-rat-cortical-neurons-are-resistant-to-acid-induced-cell-death
#9
Zoé Husson, Ewan St John Smith
Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+ permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are long-lived, fossorial, eusocial rodents that display remarkable behavioral/cellular hypoxia and hypercapnia resistance...
May 9, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29720258/t-type-calcium-channels-functionally-interact-with-spectrin-%C3%AE-%C3%AE-and-ankyrin-b
#10
Agustin Garcia-Caballero, Fang-Xiong Zhang, Victoria Hodgkinson, Junting Huang, Lina Chen, Ivana A Souza, Stuart Cain, Jennifer Kass, Sascha Alles, Terrance P Snutch, Gerald W Zamponi
This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charged cytosolic region present in the carboxy-terminus of T-type calcium channels. Deletion of this stretch of amino acids decreased binding of Cav3.1 and Cav3.2 calcium channels to spectrin (α/β) and ankyrin B and notably also reduced T-type whole cell current densities in expression systems...
May 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29720228/characterization-of-a-murine-mixed-neuron-glia-model-and-cellular-responses-to-regulatory-t-cell-derived-factors
#11
Marie Dittmer, Andrew Young, Thomas O'Hagan, George Eleftheriadis, Peter Bankhead, Yvonne Dombrowski, Reinhold J Medina, Denise C Fitzgerald
One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation...
May 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29661253/activity-dependent-decrease-in-contact-areas-between-subsurface-cisterns-and-plasma-membrane-of-hippocampal-neurons
#12
Jung-Hwa Tao-Cheng
Subsurface cistern (SSC) in neuronal soma and primary dendrites is a specialized compartment of endoplasmic reticulum (ER) that is in close apposition (10 nm) with the plasma membrane (PM). ER-PM contact areas are thought to be involved in intracellular calcium regulation. Here, structural changes of SSC in hippocampal neurons were examined by electron microscopy upon depolarization with high K+ (90 mM) or application of NMDA (50 μM) in rat dissociated cultures as well as organotypic slice cultures. The number and average length of SSC-PM contact areas in neuronal somas significantly decreased within 30 s under excitatory condition...
April 16, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29650024/vglut1-or-vglut2-mrna-positive-neurons-in-spinal-trigeminal-nucleus-provide-collateral-projections-to-both-the-thalamus-and-the-parabrachial-nucleus-in-rats
#13
Chun-Kui Zhang, Zhi-Hong Li, Yu Qiao, Ting Zhang, Ya-Cheng Lu, Tao Chen, Yu-Lin Dong, Yun-Qing Li, Jin-Lian Li
The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are strongly implicated in the sensory-discriminative and affective/emotional aspects of orofacial pain, respectively. These T-T and T-P projection fibers originate from the spinal trigeminal nucleus (Vsp). We previously determined that many vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were distributed in the Vsp of the adult rat, and most of these neurons sent their axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA-positive projection neurons exist that send their axons to both the thalamus and the parabrachial nucleus (PBN) has not been reported...
April 12, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29636075/identification-of-lncrna-expression-profiles-and-cerna-analysis-in-the-spinal-cord-of-morphine-tolerant-rats
#14
Jiali Shao, Jian Wang, Jiangju Huang, Chang Liu, Yundan Pan, Qulian Guo, Wangyuan Zou
Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment, but the mechanisms of morphine tolerance remain unclear. Recent research indicates that long noncoding RNAs (lncRNAs) might be a novel and promising target in the pathogeneses of diseases. Therefore, we hypothesized that lncRNAs might play a role in the development of morphine tolerance. Male Sprague-Dawley rats were intrathecally injected with 10 μg morphine twice daily for 7 consecutive days. The animals were then sacrificed for lncRNA microarray tests, and the results were validated by RT-qPCR...
April 10, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29631635/autophagy-is-increased-following-either-pharmacological-or-genetic-silencing-of-mglur5-signaling-in-alzheimer-s-disease-mouse-models
#15
Khaled S Abd-Elrahman, Alison Hamilton, Maryam Vasefi, Stephen S G Ferguson
Alzheimer's disease (AD) is characterized by neurotoxicity mediated by the accumulation of beta amyloid (Aβ) oligomers, causing neuronal loss and progressive cognitive decline. Genetic deletion or chronic pharmacological inhibition of mGluR5 by the negative allosteric modulator CTEP, rescues cognitive function and reduces Aβ aggregation in both APPswe/PS1ΔE9 and 3xTg-AD mouse models of AD. In late onset neurodegenerative diseases, such as AD, defects arise at different stages of the autophagy pathway. Here, we show that mGluR5 cell surface expression is elevated in APPswe/PS1ΔE9 and 3xTg-AD mice...
April 10, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29631601/biological-function-of-lemur-tyrosine-kinase-2-lmtk2-implications-in-neurodegeneration
#16
REVIEW
János Bencze, Gábor Miklós Mórotz, Woosung Seo, Viktor Bencs, János Kálmán, Christopher Charles John Miller, Tibor Hortobágyi
Neurodegenerative disorders are frequent, incurable diseases characterised by abnormal protein accumulation and progressive neuronal loss. Despite their growing prevalence, the underlying pathomechanism remains unclear. Lemur tyrosine kinase 2 (LMTK2) is a member of a transmembrane serine/threonine-protein kinase family. Although it was described more than a decade ago, our knowledge on LMTK2's biological functions is still insufficient. Recent evidence has suggested that LMTK2 is implicated in neurodegeneration...
April 10, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29551090/early-life-stress-depression-and-parkinson-s-disease-a-new-approach
#17
REVIEW
Ernest Dallé, Musa V Mabandla
This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression...
March 19, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29544505/superresolution-fluorescence-microscopy-for-3d-reconstruction-of-thick-samples
#18
Sangjun Park, Wooyoung Kang, Yeong-Dae Kwon, Jaehoon Shim, Siyong Kim, Bong-Kiun Kaang, Sungchul Hohng
Three-dimensional (3D) reconstruction of thick samples using superresolution fluorescence microscopy remains challenging due to high level of background noise and fast photobleaching of fluorescence probes. We develop superresolution fluorescence microscopy that can reconstruct 3D structures of thick samples with both high localization accuracy and no photobleaching problem. The background noise is reduced by optically sectioning the sample using line-scan confocal microscopy, and the photobleaching problem is overcome by using the DNA-PAINT (Point Accumulation for Imaging in Nanoscale Topography)...
March 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29540218/duox-mediates-ultraviolet-injury-induced-nociceptive-sensitization-in-drosophila-larvae
#19
Wijeong Jang, Minwoo Baek, Yeon Soo Han, Changsoo Kim
BACKGROUND: Nociceptive sensitization is an increase in pain perception in response to stimulus. Following brief irradiation of Drosophila larvae with UV, nociceptive sensitization occurs in class IV multiple dendritic (mdIV) neurons, which are polymodal sensory nociceptors. Diverse signaling pathways have been identified that mediate nociceptive sensitization in mdIV neurons, including TNF, Hedgehog, BMP, and Tachykinin, yet the underlying mechanisms are not completely understood. RESULTS: Here we report that duox heterozygous mutant larvae, which have normal basal nociception, exhibit an attenuated hypersensitivity response to heat and mechanical force following UV irradiation...
March 14, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29534734/vitamin-a-bio-modulates-apoptosis-via-the-mitochondrial-pathway-after-hypoxic-ischemic-brain-damage
#20
Wei Jiang, Min Guo, Min Gong, Li Chen, Yang Bi, Yun Zhang, Yuan Shi, Ping Qu, Youxue Liu, Jie Chen, Tingyu Li
Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro, and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA...
March 13, 2018: Molecular Brain
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