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https://www.readbyqxmd.com/read/28336441/chronic-stress-induced-dendritic-reorganization-and-abundance-of-synaptosomal-pka-dependent-cp-ampa-receptor-in-the-basolateral-amygdala-in-a-mouse-model-of-depression
#1
Eun-Surk Yi, Seikwan Oh, Jang-Kyu Lee, Yea-Hyun Leem
Chronic stress is a precipitating factor for disorders including depression. The basolateral amygdala (BLA) is a critical substrate that interconnects with stress-modulated neural networks to generate emotion- and mood-related behaviors. The current study shows that 3 h per day of restraint stress for 14 days caused mice to exhibit long-term depressive behaviors, manifested by disrupted sociality and despair levels, which were rescued by fluoxetine. These behavioral changes corresponded with morphological and molecular changes in BLA neurons, including chronic stress-elicited increases in arborization, dendritic length, and spine density of BLA principal neurons...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28304288/changes-in-synaptic-plasticity-and-glutamate-receptors-in-type-2-diabetic-kk-ay-mice
#2
Huajing Yin, Weiping Wang, Wenwen Yu, Jiang Li, Nan Feng, Ling Wang, Xiaoliang Wang
In the present study, the progressive alteration of cognition and the mechanisms of reduction in long-term potentiation (LTP) in spontaneous obese KK-Ay type 2 diabetic mice were investigated. In the study, 3-, 5-, and 7-month-old KK-Ay mice were used. The results indicated that KK-Ay mice showed cognitive deficits in the Morris water maze test beginning at the age of 3 months. LTP was significantly impaired in KK-Ay mice during whole study period (3 to 7 months). The above deficits were reversible at an early stage (3 to 5 months old) by diet intervention...
March 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28303090/the-inhibitory-effect-of-%C3%AE-%C3%AE-hydrolase-domain-containing-6-abhd6-on-the-surface-targeting-of-glua2-and-glua3-containing-ampa-receptors
#3
Mengping Wei, Moye Jia, Jian Zhang, Lulu Yu, Yunzhi Zhao, Yingqi Chen, Yimeng Ma, Wei Zhang, Yun S Shi, Chen Zhang
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control the biosynthesis, membrane trafficking, and synaptic targeting of AMPARs. Our previous report showed that α/β-hydrolase domain-containing 6 (ABHD6), an auxiliary subunit for AMPARs, suppresses the membrane delivery and function of GluA1-containing receptors in both heterologous cells and neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28294131/structural-and-functional-plasticity-within-the-nucleus-accumbens-and-prefrontal-cortex-associated-with-time-dependent-increases-in-food-cue-seeking-behavior
#4
Paige M Dingess, Rebecca A Darling, Rifka C Derman, Shaun S Wulff, Melissa L Hunter, Carrie R Ferrario, Travis E Brown
Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving')...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28293483/hippocampal-ampars-involve-the-central-sensitization-of-rats-with-irritable-bowel-syndrome
#5
Aiqin Chen, Yu Chen, Ying Tang, Chengjia Bao, Zizhi Cui, Meng Xiao, Chun Lin
OBJECTIVE: The roles of hippocampal AMPARs were investigated in irritable bowel syndrome (IBS)-like rats to clarify the central sensitization mechanisms. METHODS: IBS model was induced by neonatal maternal separation. The effects of AMPARs on visceral hypersensitivity were examined by the responses of abdominal muscle to colorectal distension after the bilateral intrahippocampal injections of CNQX (an AMPAR inhibitor). The expressions of hippocampal AMPARs (GluR1 and GluR2) were determined by Western blot...
March 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28290985/synaptic-transmission-and-plasticity-require-ampa-receptor-anchoring-via-its-n-terminal-domain
#6
Jake F Watson, Hinze Ho, Ingo H Greger
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process...
March 14, 2017: ELife
https://www.readbyqxmd.com/read/28285821/grasp1-regulates-synaptic-plasticity-and-learning-through-endosomal-recycling-of-ampa-receptors
#7
Shu-Ling Chiu, Graham Hugh Diering, Bing Ye, Kogo Takamiya, Chih-Ming Chen, Yuwu Jiang, Tejasvi Niranjan, Charles E Schwartz, Tao Wang, Richard L Huganir
Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity, and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28275719/a-negative-allosteric-modulator-for-%C3%AE-5-subunit-containing-gaba-receptors-exerts-a-rapid-and-persistent-antidepressant-like-action-without-the-side-effects-of-the-nmda-receptor-antagonist-ketamine-in-mice
#8
Panos Zanos, Mackenzie E Nelson, Jaclyn N Highland, Samuel R Krimmel, Polymnia Georgiou, Todd D Gould, Scott M Thompson
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28272206/limbic-encephalitis-associated-with-anti-nh2-terminal-of-%C3%AE-enolase-antibodies-a-clinical-subtype-of-hashimoto-encephalopathy
#9
Toru Kishitani, Akiko Matsunaga, Masamichi Ikawa, Kouji Hayashi, Osamu Yamamura, Tadanori Hamano, Osamu Watanabe, Keiko Tanaka, Yasunari Nakamoto, Makoto Yoneda
Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28243821/the-impact-of-short-and-long-term-exercise-on-the-expression-of-arc-and-ampars-during-evolution-of-the-6-hydroxy-dopamine-animal-model-of-parkinson-s-disease
#10
P C Garcia, C C Real, L R Britto
The loss of nigral dopaminergic neurons typical in Parkinson's disease (PD) is responsible for hyperexcitability of medium spiny neurons resulting in abnormal corticostriatal glutamatergic synaptic drive. Considering the neuroprotective effect of exercise, the changes promoted by exercise on AMPA-type glutamate receptors (AMPARs), and the role of activity-regulated cytoskeleton-associated protein (Arc) in the AMPARs trafficking, we studied the impact of short and long-term treadmill exercise during evolution of the unilateral 6-hydroxy-dopamine (6-OHDA) animal model of PD...
February 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#11
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28240305/increased-pkc-activity-and-altered-gsk3%C3%AE-nmdar-function-drive-behavior-cycling-in-hint1-deficient-mice-bipolarity-or-opposing-forces
#12
Javier Garzón-Niño, María Rodríguez-Muñoz, Elsa Cortés-Montero, Pilar Sánchez-Blázquez
Mice with histidine triad nucleotide-binding protein 1 (HINT1) deletion exhibit manic-like symptoms that evolve into depressive-like behavior in response to stressful paradigms. Molecular and electrophysiological studies have indicated that HINT1(-/-) mice exhibit increased PKC, PKA, and GSK3β activities, as well as glutamate N-methyl-D-aspartate receptor (NMDAR)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) and NR2B/NR2A subunit ratios. Pharmacological interventions stabilized their behavior but through different mechanisms...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#13
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#14
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28222692/hashimoto-s-encephalitis-associated-with-ampar2-antibodies-a-case-report
#15
Mingqin Zhu, Xuefan Yu, Caiyun Liu, Chenchen Duan, Chunxiao Li, Jie Zhu, Ying Zhang
BACKGROUND: Hashimoto's encephalitis (HE) is a rare neurological complication of Hashimoto's thyroiditis (HT), while limbic encephalitis (LE) is an autoimmune inflammatory disorder frequently associated with anti-neuronal antibodies. The glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) is important for synaptic transmission, memory, and learning. The etiology of HE remains unclear. We present a case of HE with antibodies to AMPAR2 both in the serum and cerebrospinal fluid...
February 21, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28220891/nmda-receptor-expression-in-the-thalamus-of-the-stargazer-model-of-absence-epilepsy
#16
Z Barad, D R Grattan, B Leitch
In the stargazer mouse model of absence epilepsy, altered corticothalamic excitation of reticular thalamic nucleus (RTN) neurons has been suggested to contribute to abnormal synchronicity in the corticothalamic-thalamocortical circuit, leading to spike-wave discharges, the hallmark of absence seizures. AMPA receptor expression and function are decreased in stargazer RTN, due to a mutation of AMPAR auxiliary subunit stargazin. It is unresolved and debated, however, if decreased excitation of RTN is compatible with epileptogenesis...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219790/subunit-specific-synaptic-delivery-of-ampa-receptors-by-auxiliary-chaperone-proteins-tarp%C3%AE-8-and-gsg1l-in-classical-conditioning
#17
Joyce Keifer, Neeraj K Tiwari, Leah Buse, Zhaoqing Zheng
AMPA receptor (AMPAR) trafficking has emerged as a fundamental concept for understanding mechanisms of learning and memory as well as many neurological disorders. Classical conditioning is a simple and highly conserved form of associative learning. Our studies use an ex vivo brainstem preparation in which to study cellular mechanisms underlying learning during a neural correlate of eyeblink conditioning. Two stages of AMPAR synaptic delivery underlie conditioning utilizing sequential trafficking of GluA1-containing AMPARs early in conditioning followed by replacement with GluA4 subunits later...
February 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#18
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28211453/mechanism-of-partial-agonism-in-ampa-type-glutamate-receptors
#19
Hector Salazar, Clarissa Eibl, Miriam Chebli, Andrew Plested
Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28210712/identification-of-an-epidermal-keratinocyte-ampa-glutamate-receptor-involved-in-dermatopathies-associated-with-sensory-abnormalities
#20
David Cabañero, Takeshi Irie, Marta Celorrio, Christopher Trousdale, David M Owens, David Virley, Phillip J Albrecht, Michael J Caterina, Frank L Rice, Jose A Morón
INTRODUCTION: Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid type glutamate receptors (AMPAR) in epidermal keratinocytes. METHODS: Immunohistochemical and in situ hybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes...
September 2016: Pain Reports (Baltimore, Md.)
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