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Molecular Brain

Seung-Hee Lee, Jaehoon Shim, Ye-Hwang Cheong, Sun-Lim Choi, Yong-Woo Jun, Sue-Hyun Lee, Yeon-Su Chae, Jin-Hee Han, Yong-Seok Lee, Jin-A Lee, Chae-Seok Lim, Kausik Si, Stefan Kassabov, Igor Antonov, Eric R Kandel, Bong-Kiun Kaang, Deok-Jin Jang
Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF...
October 22, 2016: Molecular Brain
Maksim Storozhuk, Elena Kondratskaya, Lyudmila Nikolaenko, Oleg Krishtal
Rapid acidification occurring during synaptic vesicle release can activate acid-sensing ion channels (ASICs) both on pre- and postsynaptic neurons. In the latter case, a fraction of postsynaptic current would be mediated by cation-selective acid-sensing ion channels. Additionally, in both cases, activation of acid-sensing ion channels could modulate synaptic strength by affecting transmitter release and/or sensitivity of postsynaptic receptors. To address potential involvement of acid-sensing ion channels in mediation/modulation of synaptic transmission at hippocampal GABAergic synapses, we studied effects of three structurally different blockers of acid-sensing ion channels on evoked postsynaptic currents using the patch-clamp technique...
October 19, 2016: Molecular Brain
Lin Cui, Wei Sun, Ming Yu, Nan Li, Li Guo, Huating Gu, Yu Zhou
Disrupted-in-schizophrenia 1(DISC1) is a promising candidate susceptibility gene for a spectrum of psychiatric illnesses that share cognitive impairments in common, including schizophrenia, bipolar disorder and major depression. Here we report that DISC1 L100P homozygous mutant shows normal anxiety- and depression-like behavior, but impaired object recognition which is prevented by administration of atypical antipsychotic drug clozapine. Ca(2+) image analysis reveals suppression of glutamate-evoked elevation of cytoplasmic [Ca(2+)] in L100P hippocampal slices...
October 12, 2016: Molecular Brain
Koki Fujimori, Toshiki Tezuka, Hiroyuki Ishiura, Jun Mitsui, Koichiro Doi, Jun Yoshimura, Hirobumi Tada, Takuya Matsumoto, Miho Isoda, Ryota Hashimoto, Nubutaka Hattori, Takuya Takahashi, Shinichi Morishita, Shoji Tsuji, Wado Akamatsu, Hideyuki Okano
Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs...
October 3, 2016: Molecular Brain
Siying Zhu, Barbara C McGrath, Yuting Bai, Xin Tang, Douglas R Cavener
PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, and modulates Ca(2+) signals-dependent working memory, we explored the role of PERK in regulating Gq protein-coupled Ca(2+) dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of a highly specific PERK inhibitor reduced the intracellular Ca(2+) rise stimulated by the activation of acetylcholine, metabotropic glutamate and bradykinin-2 receptors in primary cortical neurons...
October 1, 2016: Molecular Brain
Yao Wang, Yu-Zhang Liu, Shi-Yi Wang, Zhiru Wang
As a critical technique for dissection of synaptic and cellular mechanisms, whole-cell patch-clamp recording has become feasible for in vivo preparations including both anaesthetized and awake mammalian brains. However, compared with in vitro whole-cell recording, in vivo whole-cell recording often suffers from low success rates and high access resistance, preventing its wide application in physiological analysis of neural circuits. Here, we describe experimental procedures for achieving in vivo amphotericin B-perforated whole-cell recording as well as conventional (breakthrough) whole-cell recording from rats and mice...
September 29, 2016: Molecular Brain
Keiko Sugai, Ryuji Fukuzawa, Tomoko Shofuda, Hayato Fukusumi, Soya Kawabata, Yuichiro Nishiyama, Yuichiro Higuchi, Kenji Kawai, Miho Isoda, Daisuke Kanematsu, Tomoko Hashimoto-Tamaoki, Jun Kohyama, Akio Iwanami, Hiroshi Suemizu, Eiji Ikeda, Morio Matsumoto, Yonehiro Kanemura, Masaya Nakamura, Hideyuki Okano
The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice...
2016: Molecular Brain
Huayang Xing, Yun-An Lim, Joyce R Chong, Jasinda H Lee, Dag Aarsland, Clive G Ballard, Paul T Francis, Christopher P Chen, Mitchell K P Lai
Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone extension, and increased CRMP2 phosphorylation may lead to axonal degeneration. Axonal and synaptic pathology is an important feature of Lewy body dementias (LBD), but the state of CRMP2 phosphorylation (pCRMP2) as well as its correlations with markers of neurodegeneration have not been studied in these dementias. Hence, we measured CRMP2 phosphorylation at Thr509, Thr514 and Ser522, as well as markers of β-amyloid (Aβ), tau-phosphorylation, α-synuclein and synaptic function in the postmortem neocortex of a longitudinally assessed cohort of LBD patients characterized by low (Parkinson's disease dementia, PDD) and high (dementia with Lewy bodies, DLB) burden of Alzheimer type pathology...
2016: Molecular Brain
Alejandro Medrano-Fernández, Angel Barco
The current view of neuroplasticity depicts the changes in the strength and number of synaptic connections as the main physical substrate for behavioral adaptation to new experiences in a changing environment. Although transcriptional regulation is known to play a role in these synaptic changes, the specific contribution of activity-induced changes to both the structure of the nucleus and the organization of the genome remains insufficiently characterized. Increasing evidence indicates that plasticity-related genes may work in coordination and share architectural and transcriptional machinery within discrete genomic foci...
2016: Molecular Brain
Li-Qing Ma, Li Ning, Zhiru Wang, Ying-Wei Wang
Anterior cingulate cortex (ACC) is known to participate in numerous brain functions, such as memory storage, emotion, attention, as well as perception of acute and chronic pain. ACC-dependent brain functions often rely on ACC processing of various forms of environmental information. To understand the neural basis of ACC functions, previous studies have investigated ACC responses to environmental stimulation, particularly complex sensory stimuli as well as award and aversive stimuli, but this issue remains to be further clarified...
2016: Molecular Brain
Jung Ho Lee, Eun Jang Yoon, Jeho Seo, Adriana Kavoussi, Yong Eun Chung, Sung Phil Chung, Incheol Park, Chul Hoon Kim, Je Sung You
Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1...
2016: Molecular Brain
Edleusa M L Batista, Juliana G Doria, Talita H Ferreira-Vieira, Juliana Alves-Silva, Stephen S G Ferguson, Fabricio A Moreira, Fabiola M Ribeiro
The metabotropic glutamate receptor 5 (mGluR5) and the cannabinoid receptor 1 (CB1) exhibit a functional interaction, as CB1 regulates pre-synaptic glutamate release and mGluR5 activation increases endocannabinoid synthesis at the post-synaptic site. Since both mGluR5 and CB1 promote neuroprotection, we delineated experiments to investigate a possible link between CB1 and mGluR5 activation in the induction of neuroprotection using primary cultured corticostriatal neurons. We find that either the pharmacological blockade or the genetic ablation of either mGluR5 or CB1 can abrogate both CB1- and mGluR5-mediated neuroprotection against glutamate insult...
2016: Molecular Brain
Yanfang Rui, James Q Zheng
Small oligomeric forms of amyloid-β (Aβ) are believed to be the culprit for declined brain functions in AD in part through their impairment of neuronal trafficking and synaptic functions. However, the precise cellular actions of Aβ oligomers and underlying mechanisms in neurons remain to be fully defined. Previous studies have identified mitochondria as a major target of Aβ toxicity contributing to early cognitive decline and memory loss in neurodegenerative diseases including Alzheimer's disease (AD). In this study, we report that Aβ oligomers acutely elicit distinct effects on the transport and integrity of mitochondria...
2016: Molecular Brain
Qun-Yong Zhou, Katherine J Burton, Matthew L Neal, Yu Qiao, Anumantha G Kanthasamy, Yanjun Sun, Xiangmin Xu, Yuanye Ma, Xiaohan Li
The temporal organization of activity/rest or sleep/wake rhythms for mammals is regulated by the interaction of light/dark cycle and circadian clocks. The neural and molecular mechanisms that confine the active phase to either day or night period for the diurnal and the nocturnal mammals are unclear. Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive retinal ganglion cells, and the expression of prokineticin 2 in the intrinsically photosensitive retinal ganglion cells is oscillatory in a clock-dependent manner...
2016: Molecular Brain
Christine Luckhart, Tristan J Philippe, Brice Le François, Faranak Vahid-Ansari, Sean D Geddes, Jean-Claude Béïque, Diane C Lagace, Mireille Daigle, Paul R Albert
The C (-1019) G rs6295 promoter polymorphism of the serotonin-1A (5-HT1A) receptor gene is associated with major depression in several but not all studies, suggesting that compensatory mechanisms mediate resilience. The rs6295 risk allele prevents binding of the repressor Deaf1 increasing 5-HT1A receptor gene transcription, and the Deaf1-/- mouse model shows an increase in 5-HT1A autoreceptor expression. In this study, Deaf1-/- mice bred on a mixed C57BL6-BALB/c background were compared to wild-type littermates for 5-HT1A autoreceptor function and behavior in males and females...
2016: Molecular Brain
Cristina Borralleras, Susana Mato, Thierry Amédée, Carlos Matute, Christophe Mulle, Luis A Pérez-Jurado, Victoria Campuzano
Mice heterozygous for a complete deletion (CD) equivalent to the most common deletion found in individuals with Williams-Beuren syndrome (WBS) recapitulate relevant features of the neurocognitive phenotype, such as hypersociability, along with some neuroanatomical alterations in specific brain areas. However, the pathophysiological mechanisms underlying these phenotypes still remain largely unknown. We have studied the synaptic function and cognition in CD mice using hippocampal slices and a behavioral test sensitive to hippocampal function...
2016: Molecular Brain
Zhen Xu, Xiao-Ai Lv, Qun Dai, Yu-Qing Ge, Jie Xu
Metabolic defects and neuronal apoptosis initiated by traumatic brain injury (TBI) contribute to subsequent neurodegeneration. They are all regulated by mechanisms centered around mitochondrion. Type-1 cannabinoid receptor (CB1) is a G-protein coupled receptor (GPCR) enriched on neuronal plasma membrane. Recent evidences point to the substantial presence of CB1 receptors on neuronal mitochondrial outer membranes (mtCB1) and the activation of mtCB1 influences aerobic respiration via inhibiting mitochondrial cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/complex I pathway...
2016: Molecular Brain
Connie Cheng, Sally K M Lau, Laurie C Doering
Astrocytes are key participants in various aspects of brain development and function, many of which are executed via secreted proteins. Defects in astrocyte signaling are implicated in neurodevelopmental disorders characterized by abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP) from astrocytes is associated with delayed dendrite maturation and improper synapse formation; however, the effect of astrocyte-derived factors on the development of neurons is not known...
2016: Molecular Brain
Ting-Ting Zhang, Feng-Yan Shen, Li-Qing Ma, Wen Wen, Bin Wang, Yuan-Zhi Peng, Zhi-Ru Wang, Xuan Zhao
Itch and pain share similar mechanisms. It has been well documented that the anterior cingulate cortex (ACC) is important for pain-related perception. ACC has also been approved to be a potential pruritus-associated brain region. However, the mechanism of sensitization in pruriceptive neurons in the ACC is not clear. In current study, a chronic itch model was established by diphenylcyclopropenone (DCP) application. We found that both the frequency and amplitude of miniature excitatory postsynaptic currents in the ACC were enhanced after the formation of chronic itch...
2016: Molecular Brain
Moonseok Choi, Sangzin Ahn, Eun-Jeong Yang, Hyunju Kim, Young Hae Chong, Hye-Sun Kim
Astrocytes have been reported to exist in two states, the resting and the reactive states. Morphological changes in the reactive state of astrocytes include an increase in thickness and number of processes, and an increase in the size of the cell body. Molecular changes also occur, such as an increase in the expression of glial fibrillary acidic protein (GFAP). However, the morphological and molecular changes during the process of learning and memory have not been elucidated. In the current study, we subjected Fvb/n mice to contextual fear conditioning, and checked for morphological and molecular changes in astrocytes...
2016: Molecular Brain
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