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Bdnf nmda receptor

Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
Bok Soon Go, Sarah M Barry, Jacqueline F McGinty
Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between TrkB receptors and NMDA receptors, leading to ERK activation...
October 17, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Li-Na Yu, Li-Hong Sun, Min Wang, Min Yan
Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity...
2016: Journal of Zhejiang University. Science. B
Ashley E Lepack, Eunyoung Bang, Boyoung Lee, Jason M Dwyer, Ronald S Duman
Recent preclinical and clinical studies demonstrate that three functionally different compounds, the NMDA receptor channel blocker ketamine, mGlu2/3 receptor antagonist LY341495, and NMDA receptor glycine site agent GLYX-13 produce rapid and long lasting antidepressant effects. Furthermore, these agents are reported to stimulate ERK and mTORC1 signaling in brain. Here we used rat primary cortical culture neurons to further examine the cellular actions of these agents. The results demonstrate that low concentrations of all three compounds rapidly increase levels of the phosphorylated and activated forms of ERK and a downstream target of mTORC1, p70S6 kinase, in a concentration and time dependent manner...
December 2016: Neuropharmacology
Ernest Palomer, Adrián Martín-Segura, Shishir Baliyan, Tariq Ahmed, Detlef Balschun, Cesar Venero, Mauricio G Martin, Carlos G Dotti
Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation...
September 13, 2016: Cell Reports
Qingqing Qi, Feixue Chen, Wenxue Zhang, Peng Wang, Yanqing Li, Xiuli Zuo
BACKGROUND AND AIMS: N-methyl-D-aspartate receptor (NMDAR) in brain, spinal cord and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS). METHODS: The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and western blot, and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire...
August 30, 2016: Journal of Gastroenterology and Hepatology
Lidawani Lambuk, Azliana Jusnida Ahmad Jafri, Natasha Najwa Nor Arfuzir, Igor Iezhitsa, Renu Agarwal, Khairul Nizam Bin Rozali, Puneet Agarwal, Nor Salmah Bakar, Methil Kannan Kutty, Ahmad Pauzi Md Yusof, Anna Krasilnikova, Alexander Spasov, Alexander Ozerov, Nafeeza Mohd Ismail
Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients. The purpose of the present study was to examine the potential neuroprotective effect of Mg acetyltaurate (MgAT) on RGC death induced by NMDA...
August 27, 2016: Neurotoxicity Research
Raeesah Maqsood, Trevor W Stone
Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias...
August 23, 2016: Neurochemical Research
Andres Stucky, Kalindi P Bakshi, Eitan Friedman, Hoau-Yan Wang
Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor-NR1 subunit as well as proBDNF and BDNF...
2016: PloS One
Bangkun Yang, Ji-Chun Zhang, Mei Han, Wei Yao, Chun Yang, Qian Ren, Min Ma, Qian-Xue Chen, Kenji Hashimoto
RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression. OBJECTIVE: We compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model. RESULTS: In the tail suspension and forced swimming tests, R-ketamine (10 mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i...
October 2016: Psychopharmacology
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
Cristina Lao-Peregrín, Jesús Javier Ballesteros, Miriam Fernández, Alfonsa Zamora-Moratalla, Ana Saavedra, María Gómez Lázaro, Esther Pérez-Navarro, Deborah Burks, Eduardo D Martín
Caffeine has cognitive-enhancing properties with effects on learning and memory, concentration, arousal and mood. These effects imply changes at circuital and synaptic level, but the mechanism by which caffeine modifies synaptic plasticity remains elusive. Here we report that caffeine, at concentrations representing moderate to high levels of consumption in humans, induces an NMDA receptor-independent form of LTP (CAF LTP) in the CA1 region of the hippocampus by promoting calcium-dependent secretion of BDNF, which subsequently activates TrkB-mediated signaling required for the expression of CAF LTP...
July 25, 2016: Addiction Biology
Xin Gao, Fu-Zhi Zhuang, Shou-Jun Qin, Li Zhou, Yun Wang, Qing-Feng Shen, Mei Li, Michelle Villarreal, Lauren Benefield, Shu-Ling Gu, Teng-Fei Ma
Cognitive impairment is a common adverse effect of electroconvulsive therapy (ECT) during treatment for severe depression. Dexmedetomidine (DEX), a sedative-anesthetic drug, is used to treat post-ECT agitation. However, it is not known if DEX can protect against ECT-induced cognitive impairments. To address this, we used chronic unpredictable mild stress (CUMS) to establish a model of depression for ECT treatment. Our Morris water maze and sucrose preference test results suggest that DEX alleviates ECT-induced learning and memory impairments without altering the antidepressant efficacy of ECT...
September 30, 2016: Psychiatry Research
Alessio Travaglia, Reto Bisaz, Eric S Sweet, Robert D Blitzer, Cristina M Alberini
Episodic memories formed during the first postnatal period are rapidly forgotten, a phenomenon known as 'infantile amnesia'. In spite of this memory loss, early experiences influence adult behavior, raising the question of which mechanisms underlie infantile memories and amnesia. Here we show that in rats an experience learned during the infantile amnesia period is stored as a latent memory trace for a long time; indeed, a later reminder reinstates a robust, context-specific and long-lasting memory. The formation and storage of this latent memory requires the hippocampus, follows a sharp temporal boundary and occurs through mechanisms typical of developmental critical periods, including the expression switch of the NMDA receptor subunits from 2B to 2A, which is dependent on brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptor 5 (mGluR5)...
September 2016: Nature Neuroscience
E M Meylan, L Breuillaud, T Seredenina, P J Magistretti, O Halfon, R Luthi-Carter, J-R Cardinaux
Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice...
2016: Translational Psychiatry
Deqiang Jing, Francis S Lee, Ipe Ninan
The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in several neuropsychiatric disorders. Consistent with the potential role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF Val66Met polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medial prefrontal cortex and the central amygdala. However, it is unknown whether the BDNF Val66Met polymorphism affects synapses in the dorsal striatum, which depends on cortical afferents for BDNF...
July 1, 2016: Neuropharmacology
Yumei Ran, Biao Yan, Zhuqing Li, Yinyi Ding, Yonghui Shi, Guowei Le
Dietary modifications have been shown to contribute to the physical and mental diseases. Oxidative modifications of protein can be easily found in protein-rich food such as meat and milk products. Previous studies mainly focus on the consequences of lipid oxidation products intake in vivo, but the effects of protein oxidation products consumption have been largely neglected. Oxidants have been shown to play an important role in aging and neurodegenerative diseases. Dityrosine is the oxidated product of tyrosine residues in protein which is considered as a biomarker for oxidative stress, but the potential deleterious effects of dityrosine are unknown...
October 1, 2016: Physiology & Behavior
Hyun-Bum Kim, Eun-Sang Hwang, Ga-Young Choi, Seok Lee, Tae-Suk Park, Cheol-Won Lee, Eun-Suk Lee, Young-Choong Kim, Sang Seong Kim, Sung-Ok Lee, Ji-Ho Park
ESP-102, an extract from Angelica gigas, Saururus chinensis, and Schisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivities in vitro and in vivo studies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP), indicating the induction of long-term potentiation (LTP), in the presence of ESP-102...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Amene Saghazadeh, Shadi A Esfahani, Nima Rezaei
INTRODUCTION: Heterogeneity of therapeutic response to brain stimulation techniques has inspired scientists to uncover the secrets to success or failure of these projects. Genetic polymorphisms are one of the major causes of this heterogeneity. AREAS COVERED: More than twenty genetic variants within more than ten genes (e.g. BDNF, COMT, DRD2, TRPV1, 5-HT1A, 5-HHT, P2RX7, VEGF, TPH1, TPH2, ACE, APOE, GNB3, NET, NMDA receptors, and RGS4) have been investigated, among which the BDNF gene and its polymorphism, Val66Met, is the best documented variant...
September 2016: Expert Review of Neurotherapeutics
Ya-Chao Wang, Eduardo H Sanchez-Mendoza, Thorsten R Doeppner, Dirk M Hermann
The NMDA antagonist memantine preferentially inhibits extrasynaptic NMDA receptors, which are overactivated upon stroke and thought to disturb neuroplasticity. We hypothesized that memantine enhances post-ischemic neurological recovery, brain remodeling, and plasticity. C57BL6/j mice were exposed to intraluminal middle cerebral artery occlusion. Starting 72 hours post-stroke, vehicle or memantine (4 or 20 mg/kg/day) were subcutaneously delivered over 28 days. Neurological recovery, perilesional tissue remodeling and contralesional pyramidal tract plasticity were evaluated over 49 days...
May 11, 2016: Journal of Cerebral Blood Flow and Metabolism
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