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CREB AND NMDAR

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https://www.readbyqxmd.com/read/30501045/flux-independent-nmdar-signaling-molecular-mediators-cellular-functions-and-complexities
#1
REVIEW
Pavel Montes de Oca Balderas
The glutamate (Glu) N-methyl-d-aspartate (NMDA) receptor (NMDAR) plays a critical role in synaptic communication given mainly by its ionotropic function that permeates Ca2+ . This in turn activates calmodulin that triggers CaMKII, MAPK, CREB, and PI3K pathways, among others. However, NMDAR signaling is more complex. In the last two decades several groups have shown that the NMDAR also elicits flux-independent signaling (f-iNMDARs). It has been demonstrated that agonist (Glu or NMDA) or co-agonist (Glycine or d-Serine) bindings initiate intracellular events, including conformational changes, exchange of molecular interactions, release of second messengers, and signal transduction, that result in different cellular events including endocytosis, LTD, cell death, and neuroprotection, among others...
November 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30233298/prenatal-deltamethrin-exposure-induced-cognitive-impairment-in-offspring-is-ameliorated-by-memantine-through-nmdar-bdnf-signaling-in-hippocampus
#2
Chao Zhang, Qinghua Xu, Xia Xiao, Weihao Li, Qiang Kang, Xiong Zhang, Tinghua Wang, Yan Li
Background: Pyrethroids have been widely used in residential and agricultural areas. However, little is known about the effects of prenatal exposure to deltamethrin on cognition in early development of offspring. In this study, the effects of prenatal exposure to deltamethrin on learning and memory abilities, N -methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response element binding protein (pCREB) in the hippocampus of offspring rats were investigated...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/30055776/stigmasterol-activates-cdc42-arp2-and-erk1-2-creb-pathways-to-enrich-glutamatergic-synapses-in-cultures-of-brain-neurons
#3
Md Nazmul Haque, Mohammad Maqueshudul Haque Bhuiyan, Il Soo Moon
The naturally occurring phytosterol stigmasterol (ST) ameliorates scopolamine-induced memory impairment and promotes neuritogenesis and synaptogenesis. Therefore, in this study, we investigated the hypothesis that ST promotes spinogenesis and the formation of glutamatergic synapses and thus improves memory in cultured rat hippocampal neurons. Immunoblots showed that ST activated extracellular signal-regulated kinase 1/2 (Erk1/2) and cAMP response element binding protein (Creb), and upregulated actin-related protein 2 (Arp2) and cell division cycle 42 (Cdc42), central components in actin organization and spine head development...
August 2018: Nutrition Research
https://www.readbyqxmd.com/read/29960099/trx-1-ameliorates-learning-and-memory-deficits-in-mptp-induced-parkinson-s-disease-model-in-mice
#4
Xianwen Zhang, Liping Bai, Se Zhang, Xiaoshuang Zhou, Ye Li, Jie Bai
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and protects neurons from various injuries. Our previous study has shown that Trx-1 overexpression attenuates movement disorder in PD. However, whether Trx-1 ameliorates cognitive deficits in PD is still unknown. In the present study, we investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice...
June 28, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29895894/nmdar-independent-camp-dependent-antidepressant-actions-of-ketamine
#5
Nathan H Wray, Jeffrey M Schappi, Harinder Singh, Nicolas B Senese, Mark M Rasenick
Ketamine produces rapid and robust antidepressant effects in depressed patients within hours of administration, often when traditional antidepressant compounds have failed to alleviate symptoms. We hypothesized that ketamine would translocate Gαs from lipid rafts to non-raft microdomains, similarly to other antidepressants but with a distinct, abbreviated treatment duration. C6 glioma cells were treated with 10 µM ketamine for 15 min, which translocated Gαs from lipid raft domains to non-raft domains...
June 12, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29804319/microrna-219-decreases-hippocampal-long-term-potentiation-inhibition-and-hippocampal-neuronal-cell-apoptosis-in-type-2-diabetes-mellitus-mice-by-suppressing-the-nmdar-signaling-pathway
#6
Ling Zhang, Zheng-Wen Chen, Shu-Fen Yang, Muyasi Shaer, Ying Wang, Jun-Jie Dong, Beili Jiapaer
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%-95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA-219 (miR-219) on inhibition of long-term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway regulation. METHODS: The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured...
May 27, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29736613/inhibition-of-acid-sensing-ion-channel-3-aggravates-seizures-by-regulating-nmdar-function
#7
Qian Cao, Zhe-Man Xiao, Xi Wang, Chao Weng, Man Ding, Fan Zhu, Zu-Neng Lu
The existing data about whether acid sensing ion channels (ASICs) are proconvulsant or anticonvulsant are controversial. Particularly, acid sensing ion channel 3 (ASIC3) is the most sensitive to extracellular pH and has the characteristic ability to generate a biphasic current, but few studies have focused on the role of ASIC3 in seizure. Here we found ASIC3 expression was increased in the hippocampus of pilocarpine induced seizure rats, as well as in hippocampal neuronal cultures undergoing epileptiform discharge elicited by Mg2+ -free media...
May 7, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29648983/enhancement-of-brain-d-serine-mediates-recovery-of-cognitive-function-after-traumatic-brain-injury
#8
Sigal Liraz-Zaltsman, Barbara Slusher, Dana Atrakchi-Baranes, Kineret Rosenblatt, Yael Friedman Levi, Efrat Kesner, Alcino J Silva, Anat Biegon, Esther Shohami
Cognitive deficits, especially memory loss, are common and devastating neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may persist for years and may be accompanied by increased risk of developing early- onset dementia. Past attempts to reverse the neuropathological effects of brain injury with glutamate-N-methyl-d-aspartate (NMDA) antagonists failed to show any benefits or worsened the outcome, suggesting that activation, rather than blockage, of the NMDA receptor (NMDAR) may be useful in the subacute period after TBI and stroke...
July 15, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29578035/ras-inhibitor-s-trans-trans-farnesylthiosalicylic-acid-enhances-spatial-memory-and-hippocampal-long-term-potentiation-via-up-regulation-of-nmda-receptor
#9
Ya Wang, Tingting Chen, Zihao Yuan, Yajie Zhang, Baofeng Zhang, Liandong Zhao, Ling Chen
Statins by reducing farnesyl-pyrophosphate or farnesyl transferase inhibitors have been demonstrated to enhance spatial memory and long-term potentiation (LTP). The objective of this study was to investigate effects of the synthetic Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) on spatial cognitive function in adult mice, synaptic plasticity in hippocampal CA1 regions, and NMDA receptor (NMDAr) activity of pyramidal cells. Here, we show that administering FTS (5 mg/kg, i.p.) enhanced spatial cognitive performance, as assessed via Morris water maze and Y-maze tests...
September 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29577983/age-related-nmda-signaling-alterations-in-sod2-deficient-mice
#10
Francisco J Carvajal, Rodrigo G Mira, Maximiliano Rovegno, Alicia N Minniti, Waldo Cerpa
Oxidative stress affects the survival and function of neurons. Hence, they have a complex and highly regulated machinery to handle oxidative changes. The dysregulation of this antioxidant machinery is associated with a wide range of neurodegenerative conditions. Therefore, we evaluated signaling alterations, synaptic properties and behavioral performance in 2 and 6-month-old heterozygous manganese superoxide dismutase knockout mice (SOD2+/- mice). We found that their low antioxidant capacity generated direct oxidative damage in proteins, lipids, and DNA...
June 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/29567262/oxidative-stress-evoked-damages-leading-to-attenuated-memory-and-inhibition-of-nmdar-camkii-erk-creb-signalling-on-consumption-of-aspartame-in-rat-model
#11
Ashok Iyaswamy, Ananth Kumar Kammella, Citarasu Thavasimuthu, Wankhar Wankupar, Wankhar Dapkupar, Sambantham Shanmugam, Ravindran Rajan, Sheeladevi Rathinasamy
Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposes to investigate whether long term (90 days) aspartame (40 mg/kg b.wt) administration could induce oxidative stress and alter the memory in Wistar strain male albino rats. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included as a model to study the effects of aspartame. Wistar strain albino rats were administered with aspartame (40 mg/kg b...
April 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29461008/propofol-exposure-during-early-gestation-impairs-learning-and-memory-in-rat-offspring-by-inhibiting-the-acetylation-of-histone
#12
Jiamei Lin, Shengqiang Wang, Yunlin Feng, Weihong Zhao, Weilu Zhao, Foquan Luo, Namin Feng
Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29172439/altered-creb-binding-to-activity-dependent-genes-in-serine-racemase-deficient-mice-a-mouse-model-of-schizophrenia
#13
Darrick T Balu, Joseph T Coyle
cAMP-response-element-binding protein (CREB) is a transcription factor ubiquitously expressed in the brain that regulates neuroplasticity by modulating gene expression. The influx of calcium through N-methyl-d-aspartate receptors (NMDARs) is a well-defined mechanism that leads to the increased expression of CREB-dependent genes, including brain derived neurotrophic factor (BDNF), microRNA-132, and activity-regulated cytoskeleton-associated protein (Arc). These molecules are implicated in the pathophysiology of schizophrenia...
September 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28919534/glutamate-induced-rapid-induction-of-arc-arg3-1-requires-nmda-receptor-mediated-phosphorylation-of-erk-and-creb
#14
Tao Chen, Jie Zhu, Li-Kun Yang, Yi Feng, Wei Lin, Yu-Hai Wang
Arc/Arg3.1 is a unique immediate early gene whose expression is highly dynamic and correlated with various forms of synaptic plasticity. Many previous reports highlight the complexity of mechanisms that regulate Arc/Arg3.1 expression in neurons. In the present study, the expression and regulation of Arc/Arg3.1 after glutamate treatment in primary cultured cortical neurons were investigated. We found that both Arc/Arg3.1 mRNA and Arc/Arg3.1 protein dynamically increased within 24h after glutamate treatment. The results of immunostaining showed that abundant amounts of Arc/Arg3...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28746067/perturbing-nr2b-psd-95-interaction-relieves-neuropathic-pain-by-inactivating-camkii-creb-signaling
#15
Fangxia Xu, Xin Zhao, Lin Liu, Jia Song, Yingjun Zhu, Shuaishuai Chu, Xueming Shao, Xiuxiu Li, Zhengliang Ma, Xiaoping Gu
Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting...
September 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/28565929/effects-of-acute-and-chronic-exposure-to-both-900-mhz-and-2100-mhz-electromagnetic-radiation-on-glutamate-receptor-signaling-pathway
#16
Çiğdem Gökçek-Saraç, Hakan Er, Ceren Kencebay Manas, Deniz Kantar Gok, Şükrü Özen, Narin Derin
PURPOSE: To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100 MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes - including PKA, CaMKIIα, CREB, and p44/42 MAPK - from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways. MATERIALS AND METHODS: Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100 MHz RF-EMR for 2 h/day for acute (1 week) or chronic (10 weeks), respectively...
September 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28554200/the-memory-enhancing-effects-of-liquiritigenin-by-activation-of-nmda-receptors-and-the-creb-signaling-pathway-in-mice
#17
Yong-Hyun Ko, Seung-Hwan Kwon, Ji-Young Hwang, Kyung-In Kim, Jee-Yeon Seo, Thi-Lien Nguyen, Seok-Yong Lee, Hyoung-Chun Kim, Choon-Gon Jang
Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ...
March 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28160495/nmda-receptor-subunit-composition-controls-dendritogenesis-of-hippocampal-neurons-through-camkii-creb-p-and-h3k27ac
#18
Fernando J Bustos, Nur Jury, Pablo Martinez, Estibaliz Ampuero, Matias Campos, Sebastian Abarzúa, Karen Jaramillo, Susanne Ibing, Muriel D Mardones, Henny Haensgen, Julia Kzhyshkowska, Maria Florencia Tevy, Rachael Neve, Magdalena Sanhueza, Lorena Varela-Nallar, Martín Montecino, Brigitte van Zundert
Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins...
December 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27789382/effects-of-sesamin-on-motor-and-memory-deficits-in-an-mptp-lesioned-mouse-model-of-parkinson-s-disease-treated-with-l-dopa
#19
T T Zhao, K S Shin, K S Kim, H J Park, H J Kim, K E Lee, M K Lee
The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg)...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27664298/nmdar-dependent-intracellular-responses-associated-with-cocaine-conditioned-place-preference-behavior
#20
Stephanie K Nygard, Anthony Klambatsen, Bailey Balouch, Vanya Quinones-Jenab, Shirzad Jenab
The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and ΔFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug's rewarding effects, to study the role of these signaling pathways in cocaine-context associations...
January 15, 2017: Behavioural Brain Research
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