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https://www.readbyqxmd.com/read/29780879/altered-cerebellar-short-term-plasticity-but-no-change-in-postsynaptic-ampa-type-glutamate-receptors-in-a-mouse-model-of-juvenile-batten-disease
#1
Dorota Studniarczyk, Elizabeth L Needham, Hannah M Mitchison, Mark Farrant, Stuart G Cull-Candy
Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study, we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knock-out mice. In Cln3 Δ ex1-6 cells, the amplitude of AMPA-evoked whole-cell currents was unchanged...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#2
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29751227/ampa-receptor-positive-allosteric-modulators-attenuate-morphine-tolerance-and-dependence
#3
Xiaoyu Hu, Xuebi Tian, Xiao Guo, Ying He, Haijun Chen, Jia Zhou, Zaijie Jim Wang
Development of opioid tolerance and dependence hinders the use of opioids for the treatment of chronic pain. In searching for the mechanism and potential intervention for opioid tolerance and dependence, we studied the action of two positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR PAMs). In mice treated with morphine (100 mg/kg, s.c.), acute morphine tolerance and dependence developed in 4-6 h. Treatment with aniracetam, a well-established AMPAR PAM, was able to completely prevent and reverse the development of acute antinociceptive tolerance to morphine...
April 25, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29738885/regulation-of-seizure-induced-mecp2-ser421-phosphorylation-in-the-developing-brain
#4
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29738844/removal-of-area-ca3-from-hippocampal-slices-induces-postsynaptic-plasticity-at-schaffer-collateral-synapses-that-normalizes-ca1-pyramidal-cell-discharge
#5
Theodore C Dumas, Michael R Uttaro, Carolina Barriga, Tiffany Brinkley, Maryam Halavi, Susan N Wright, Michele Ferrante, Rebekah C Evans, Sarah L Hawes, Erin M Sanders
Neural networks that undergo acute insults display remarkable reorganization. This injury related plasticity is thought to permit recovery of function in the face of damage that cannot be reversed. Previously, an increase in the transmission strength at Schaffer collateral to CA1 pyramidal cell synapses was observed after long-term activity reduction in organotypic hippocampal slices. Here we report that, following acute preparation of adult rat hippocampal slices and surgical removal of area CA3, input to area CA1 was reduced and Schaffer collateral synapses underwent functional strengthening...
May 5, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29715286/retraction-the-early-stage-formation-of-pi3k-ampar-glur2-subunit-complex-facilitates-the-long-term-neuroprotection-induced-by-propofol-post-conditioning-in-rats
#6
https://www.readbyqxmd.com/read/29712715/nmdar-dependent-argonaute-2-phosphorylation-regulates-mirna-activity-and-dendritic-spine-plasticity
#7
Dipen Rajgor, Thomas M Sanderson, Mascia Amici, Graham L Collingridge, Jonathan G Hanley
MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), underpinning a powerful mechanism for fine-tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins...
April 30, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29708744/positive-modulators-of-the-n-methyl-d-aspartate-receptor-structure-activity-relationship-study-on-steroidal-3-hemiesters
#8
Barbora Krausova, Barbora Slavikova, Michaela Nekardova, Pavla Hubalkova, Vojtech Vyklicky, Hana Chodounska, Ladislav Vyklicky, Eva Kudova
Here, we report the synthesis of pregn-5-ene and androst-5-ene dicarboxylic acid esters and explore the structure-activity relationship (SAR) for their modulation of N-methyl- D-aspartate receptors (NMDARs). All compounds were positive modulators of recombinant GluN1/GluN2B receptors (EC50 varying from 1.8 to 151.4 µM and Emax varying from 48 to 452 %). Moreover, 10 compounds were found to be more potent GluN1/GluN2B receptor modulators than endogenous pregnenolone sulfate (EC50 = 21.7 µM). The SAR study revealed a relationship between the length of the residues at carbon C-3 of the steroid molecule and the positive modulatory effect at GluN1/GluN2B receptors for various D-ring modifications...
April 30, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29694885/wnt-signaling-mediates-ltp-dependent-spine-plasticity-and-ampar-localization-through-frizzled-7-receptors
#9
Faye McLeod, Alessandro Bossio, Aude Marzo, Lorenza Ciani, Sara Sibilla, Saad Hannan, Gemma A Wilson, Ernest Palomer, Trevor G Smart, Alasdair Gibb, Patricia C Salinas
The structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established. Wnts are required for spine formation; however, their impact on activity-mediated spine plasticity and AMPAR localization is unknown. We found that LTP induction rapidly increased synaptic Wnt7a/b protein levels...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29676230/insights-into-the-molecular-aspects-of-neuroprotective-bacoside-a-and-bacopaside-i
#10
Vini C Sekhar, Gayathri Viswanathan, Sabulal Baby
Bacopa monnieri, commonly known as Brahmi, has been extensively used as a neuromedicine for various disorders such as anxiety, depression and memory loss. Chemical characterization studies revealed the major active constituents of the herb as the triterpenoid saponins, bacosides. Bacoside A, the vital neuroprotective constituent, is composed of four constituents viz., bacoside A3, bacopaside II, jujubogenin isomer of bacopasaponin C (bacopaside X) and bacopasaponin C. B. monnieri extracts as well as bacosides successfully establish a healthy antioxidant environment in various tissues especially in liver and brain...
April 19, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29675583/do-alcohol-related-ampa-type-glutamate-receptor-adaptations-promote-intake
#11
F Woodward Hopf, Regina A Mangieri
Ionotropic glutamate receptors (AMPA, NMDA, and kainate receptors) play a central role in excitatory glutamatergic signaling throughout the brain. As a result, functional changes, especially long-lasting forms of plasticity, have the potential to profoundly alter neuronal function and the expression of adaptive and pathological behaviors. Thus, alcohol-related adaptations in ionotropic glutamate receptors are of great interest, since they could promote excessive alcohol consumption, even after long-term abstinence...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29623602/inhibition-of-astrocyte-connexin-43-channels-facilitates-the-differentiation-of-oligodendrocyte-precursor-cells-under-hypoxic-conditions-in-vitro
#12
Qiong Wang, Zhen Wang, Yeye Tian, Huaqiu Zhang, Yongkang Fang, Zhiyuan Yu, Wei Wang, Minjie Xie, Fengfei Ding
Oligodendrocyte precursor cells (OPCs) proliferation and differentiation are essential for remyelination after white matter injury. Astrocytes could promote oligodendrogenesis after white matter damage whereas the underlying mechanisms are unknown. In this study, the role of astrocytic connexin43 (Cx43) hemichannels involved in OPC proliferation and differentiation in chronic hypoxia was evaluated. In an astrocyte-OPC co-culture chronic hypoxia model, OPCs became proliferative but failed to mature into oligodendrocytes...
April 5, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29614651/amyloid-%C3%AE-induces-ampa-receptor-ubiquitination-and-degradation-in-primary-neurons-and-human-brains-of-alzheimer-s-disease
#13
Yanmin Zhang, Ouyang Guo, Yuda Huo, Guan Wang, Heng-Ye Man
As the primary mediator for synaptic transmission, AMPA receptors (AMPARs) are crucial for synaptic plasticity and higher brain functions. A downregulation of AMPAR expression has been indicated as one of the early pathological molecular alterations in Alzheimer's disease (AD), presumably via amyloid-β (Aβ). However, the molecular mechanisms leading to the loss of AMPARs remain less clear. We report that in primary neurons, application of Aβ triggers AMPAR internalization accompanied with a decrease in cell-surface AMPAR expression...
January 24, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29601943/lung-injury-depresses-glutamatergic-synaptic-transmission-in-the-nucleus-tractus-solitarii-via-discrete-age-dependent-mechanisms-in-neonatal-rats
#14
David G Litvin, Thomas E Dick, Corey B Smith, Frank J Jacono
Transition periods (TPs) are brief stages in CNS development where neural circuits can exhibit heightened vulnerability to pathologic conditions such as injury or infection. This susceptibility is due in part to specialized mechanisms of synaptic plasticity, which may become activated by inflammatory mediators released under pathologic conditions. Thus, we hypothesized that the immune response to lung injury (LI) mediated synaptic changes through plasticity-like mechanisms that depended on whether LI occurred just before or after a TP...
March 27, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29588966/pathogenic-potential-of-antibodies-to-the-gaba-b-receptor
#15
Anjan Nibber, Edward O Mann, Philippa Pettingill, Patrick Waters, Sarosh R Irani, Dimitri M Kullmann, Angela Vincent, Bethan Lang
GABAB receptor (GABAB R) autoantibodies have been detected in the serum of immunotherapy-responsive patients with autoimmune encephalitis. This study aimed to investigate the effect of immunoglobulin G (IgG) from a patient with GABAB R antibodies on primary neuronal cultures and acute slices of entorhinal cortex. Primary hippocampal neuronal cultures were incubated with serum immunoglobulin from patients with GABAB R or AMPA receptor (AMPAR) antibodies for up to 72 h to investigate their effect on receptor surface expression...
September 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29588465/mef2a-regulates-mglur-dependent-ampa-receptor-trafficking-independently-of-arc-arg3-1
#16
Ruth E Carmichael, Kevin A Wilkinson, Tim J Craig, Michael C Ashby, Jeremy M Henley
Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29587280/inhibition-of-cgkii-suppresses-seizure-activity-and-hippocampal-excitation-by-regulating-the-postsynaptic-delivery-of-glua1
#17
Juan Gu, Xin Tian, Wei Wang, Qin Yang, Peijia Lin, Yuanlin Ma, Yan Xiong, Demei Xu, Yanke Zhang, Yong Yang, Shanshan Lu, Zijun Lin, Jing Luo, Fei Xiao, Xuefeng Wang
BACKGROUND/AIMS: The imbalance between excitation and inhibition is a defining feature of epilepsy. GluA1 is an AMPA receptor subunit that can strengthen excitatory synaptic transmission when upregulated in the postsynaptic membrane, which has been implicated in the pathogenesis of epilepsy. cGKII, a cGMP-dependent protein kinase, regulates the GluA1 levels at the plasma membrane. METHODS: To explore the role of cGKII in epilepsy, we investigated the expression of cGKII in patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model and then performed behavioral, histological, and electrophysiological analyses by applying either a cGKII agonist or inhibitor in the hippocampus of the animal model...
March 21, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29569345/fish-oil-treatment-reduces-chronic-alcohol-exposure-induced-synaptic-changes
#18
Zhe Shi, Youna Xie, Huixia Ren, Baixuan He, Meng Wang, Jian-Bo Wan, Ti-Fei Yuan, Xiaoli Yao, Huanxing Su
Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure...
March 22, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29560257/homeostatic-synaptic-scaling-molecular-regulators-of-synaptic-ampa-type-glutamate-receptors
#19
REVIEW
Dhrubajyoti Chowdhury, Johannes W Hell
The ability of neurons and circuits to maintain their excitability and activity levels within the appropriate dynamic range by homeostatic mechanisms is fundamental for brain function. Neuronal hyperactivity, for instance, could cause seizures.  One such homeostatic process is synaptic scaling, also known as synaptic homeostasis. It involves a negative feedback process by which neurons adjust (scale) their postsynaptic strength over their whole synapse population to compensate for increased or decreased overall input thereby preventing neuronal hyper- or hypoactivity that could otherwise result in neuronal network dysfunction...
2018: F1000Research
https://www.readbyqxmd.com/read/29555855/autophagy-enhances-memory-erasure-through-synaptic-destabilization
#20
Mohammad Shehata, Kareem Abdou, Kiriko Choko, Mina Matsuo, Hirofumi Nishizono, Kaoru Inokuchi
There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be utilized to overcome these conditions...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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