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https://www.readbyqxmd.com/read/27922130/the-nmda-receptor-glun2c-subunit-controls-cortical-excitatory-inhibitory-balance-neuronal-oscillations-and-cognitive-function
#1
Subhash C Gupta, Aparna Ravikrishnan, Jinxu Liu, Zhihao Mao, Ratnamala Pavuluri, Brandon G Hillman, Pauravi J Gandhi, Dustin J Stairs, Ming Li, Rajesh R Ugale, Daniel T Monaghan, Shashank M Dravid
Despite strong evidence for NMDA receptor (NMDAR) hypofunction as an underlying factor for cognitive disorders, the precise roles of various NMDAR subtypes remains unknown. The GluN2C-containing NMDARs exhibit unique biophysical properties and expression pattern, and lower expression of GluN2C subunit has been reported in postmortem brains from schizophrenia patients. We found that loss of GluN2C subunit leads to a shift in cortical excitatory-inhibitory balance towards greater inhibition. Specifically, pyramidal neurons in the medial prefrontal cortex (mPFC) of GluN2C knockout mice have reduced mEPSC frequency and dendritic spine density and a contrasting higher frequency of mIPSCs...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917825/molecular-symmetry-constrained-systematic-search-approach-to-structure-solution-of-the-coiled-coil-srgap2-f-barx-domain
#2
Michael Sporny, Julia Guez-Haddad, David G Waterman, Michail N Isupov, Yarden Opatowsky
SRGAP2 (Slit-Robo GTPase-activating protein 2) is a cytoplasmic protein found to be involved in neuronal branching, restriction of neuronal migration and restriction of the length and density of dendritic postsynaptic spines. The extended F-BAR (F-BARx) domain of SRGAP2 generates membrane protrusions when expressed in COS-7 cells, while most F-BARs induce the opposite effect: membrane invaginations. As a first step to understand this discrepancy, the F-BARx domain of SRGAP2 was isolated and crystallized after co-expression with the carboxy domains of the protein...
December 1, 2016: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/27916859/postnatal-gene-therapy-improves-spatial-learning-despite-the-presence-of-neuronal-ectopia-in-a-model-of-neuronal-migration-disorder
#3
Huaiyu Hu, Yu Liu, Kevin Bampoe, Yonglin He, Miao Yu
Patients with type II lissencephaly, a neuronal migration disorder with ectopic neurons, suffer from severe mental retardation, including learning deficits. There is no effective therapy to prevent or correct the formation of neuronal ectopia, which is presumed to cause cognitive deficits. We hypothesized that learning deficits were not solely caused by neuronal ectopia and that postnatal gene therapy could improve learning without correcting the neuronal ectopia formed during fetal development. To test this hypothesis, we evaluated spatial learning of cerebral cortex-specific protein O-mannosyltransferase 2 (POMT2, an enzyme required for O-mannosyl glycosylation) knockout mice and compared to the knockout mice that were injected with an adeno-associated viral vector (AAV) encoding POMT2 into the postnatal brains with Barnes maze...
November 29, 2016: Genes
https://www.readbyqxmd.com/read/27916727/posttraumatic-administration-of-a-sub-anesthestic-dose-of-ketamine-exerts-neuroprotection-via-attenuating-inflammation-and-autophagy
#4
C-Q Wang, Y Ye, F Chen, W-C Han, J-M Sun, X Lu, R Guo, K Cao, M-J Zheng, L-C Liao
As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine...
December 1, 2016: Neuroscience
https://www.readbyqxmd.com/read/27909399/a-subset-of-autism-associated-genes-regulate-the-structural-stability-of-neurons
#5
REVIEW
Yu-Chih Lin, Jeannine A Frei, Michaela B C Kilander, Wenjuan Shen, Gene J Blatt
Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals' ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27909098/reversible-disruption-of-neuronal-mitochondria-by-ischemic-and-traumatic-injury-revealed-by-quantitative-two-photon-imaging-in-the-neocortex-of-anesthetized-mice
#6
Mikhail Kislin, Jeremy Sword, Ioulia V Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S Ribeiro, Leonard Khiroug, Sergei A Kirov
: Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under such pathological conditions as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries ranging from severe to mild...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909004/pea3-transcription-factors-etv4-and-etv5-are-required-for-proper-hippocampal-dendrite-development-and-plasticity
#7
Paula Aldana Fontanet, Antonella Soledad Ríos, Fernando Cruz Alsina, Gustavo Paratcha, Fernanda Ledda
The proper formation and morphogenesis of dendrites is essential to the establishment of neuronal connectivity. We report that 2 members of the Pea3 family of transcription factors, Etv4 and Etv5, are expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that they have a function in dendrite development. Here, we show that these transcription factors are physiological regulators of growth and arborization of pyramidal cell dendrites in the developing hippocampus. Gain and loss of function assays indicate that Etv4 and Etv5 are required for proper development of hippocampal dendritic arbors and spines...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27908784/cisplatin-induced-mitochondrial-dysfunction-is-associated-with-impaired-cognitive-function-in-rats
#8
Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC). We also assessed the protective effects of the antioxidant, N-acetylcysteine in mitigating these damages...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#9
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27904493/beta-2-adrenergic-receptor-activation-enhances-neurogenesis-in-alzheimer-s-disease-mice
#10
Gao-Shang Chai, Yang-Yang Wang, Amina Yasheng, Peng Zhao
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27898076/growth-hormone-biases-amygdala-network-activation-after-fear-learning
#11
B Gisabella, S Farah, X Peng, A Burgos-Robles, S H Lim, K A Goosens
Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the 'over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27897242/cortical-synaptic-and-dendritic-spine-abnormalities-in-a-presymptomatic-tdp-43-model-of-amyotrophic-lateral-sclerosis
#12
Matthew J Fogarty, Paul M Klenowski, John D Lee, Joy R Drieberg-Thompson, Selena E Bartlett, Shyuan T Ngo, Massimo A Hilliard, Mark C Bellingham, Peter G Noakes
Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43(Q331K) mutation...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881772/store-operated-calcium-channel-complex-in-postsynaptic-spines-a-new-therapeutic-target-for-alzheimer-s-disease-treatment
#13
Hua Zhang, Suya Sun, Lili Wu, Ekaterina Pchitskaya, Olga Zakharova, Klementina Fon Tacer, Ilya Bezprozvanny
: Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca(2+) influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca(2+) channel complex in hippocampal mushroom spines...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27880914/neuronal-ctcf-is-necessary-for-basal-and-experience-dependent-gene-regulation-memory-formation-and-genomic-structure-of-bdnf-and-arc
#14
Dev Sharan Sams, Stefano Nardone, Dmitriy Getselter, Dana Raz, Moran Tal, Prudhvi Raj Rayi, Hanoch Kaphzan, Ofir Hakim, Evan Elliott
CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long-term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#15
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27878209/preclinical-models-of-overwhelming-sepsis-implicate-the-neural-system-that-encodes-contextual-fear-memory
#16
Patricio T Huerta, Sergio Robbiati, Tomás Salvador Huerta, Anchal Sabharwal, Rose A Berlin, Maya Frankfurt, Bruce T Volpe
Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27876669/ginsenoside-rg1-induced-antidepressant-effects-involve-the-protection-of-astrocyte-gap-junctions-within-the-prefrontal-cortex
#17
Can Jin, Zhen-Zhen Wang, Heng Zhou, Yu-Xia Lou, Jiao Chen, Wei Zuo, Man-Tong Tian, Zhi-Qi Wang, Guo-Hua Du, Ichiro Kawahata, Tohru Yamakuni, Yi Zhang, Nai-Hong Chen, Dan-Shen Zhang
Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing neurogenesis and dendritic spine density without discernible side effects. However, the molecular mechanisms underlying Rg1 antidepressant activity remain poorly understood. As the dysfunction of gap junctions between astrocytes in the prefrontal cortex (PFC) is implicated in major depression disorder, the aim of this study was to investigate the effects of Rg1 on astrocyte gap junctions in the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1 (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the sucrose preference and forced swimming tests...
November 19, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27873505/hyperbaric-oxygen-pretreatment-improves-cognition-and-reduces-hippocampal-damage-via-p38-mitogen-activated-protein-kinase-in-a-rat-model
#18
Baisong Zhao, Yongying Pan, Zixin Wang, Haiping Xu, Xingrong Song
PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer's disease (AD) rat model. MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27872870/nanoscale-organization-of-synaptic-adhesion-proteins-revealed-by-single-molecule-localization-microscopy
#19
Ingrid Chamma, Florian Levet, Jean-Baptiste Sibarita, Matthieu Sainlos, Olivier Thoumine
The advent of superresolution imaging has created a strong need for both optimized labeling strategies and analysis methods to probe the nanoscale organization of complex biological structures. We present a thorough description of the distribution of synaptic adhesion proteins at the nanoscopic scale, namely presynaptic neurexin-[Formula: see text] ([Formula: see text]), and its two postsynaptic binding partners neuroligin-1 (Nlg1) and leucine-rich-repeat transmembrane protein 2 (LRRTM2). We monitored these proteins in the membrane of neurons by direct stochastic optical reconstruction microscopy, after live surface labeling with Alexa647-conjugated monomeric streptavidin...
October 2016: Neurophotonics
https://www.readbyqxmd.com/read/27871669/induction-and-blockade-of-adolescent-cocaine-induced-habits
#20
Lauren M DePoy, Kelsey S Zimmermann, Paul J Marvar, Shannon L Gourley
BACKGROUND: Cocaine use during adolescence increases vulnerability to drug dependence and decreases the likelihood that individuals will seek treatment as adults. Understanding how early-life cocaine exposure influences decision-making processes in adulthood is thus critically important. METHODS: Adolescent or adult mice were exposed to subchronic cocaine, then behavioral sensitivity to changes in the predictive relationship between actions and their consequences was tested...
October 6, 2016: Biological Psychiatry
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