792 results match your criteria subunit glun2b

Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing -Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice.

Front Aging Neurosci 2021 25;13:671206. Epub 2021 May 25.

Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacy, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.

P301S transgenic mice are an animal model of tauopathy and Alzheimer's disease (AD), exhibiting tau pathology and synaptic dysfunction. Cornel iridoid glycoside (CIG) is an active ingredient extracted from , a traditional Chinese herb. In the present study, the purpose was to investigate the effects and mechanisms of CIG on tau pathology and synaptic dysfunction using P301S transgenic mice. Read More

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Chronic early life social isolation affects NMDA and TrkB receptor expression in a sex-specific manner.

Neurosci Lett 2021 Jun 7:136016. Epub 2021 Jun 7.

School of Public Health Sciences, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada. Electronic address:

Exposing mammals to adverse social environments early in life can affect brain development in ways that alter adult behaviour. For example, chronic, early-life social isolation (CELSI) has been found to cause novelty-induced hyperactivity, impaired pre-pulse inhibition, and enhanced anxiety-related behaviour. Although the molecular mechanism(s) underlying the embedding of CELSI have not been fully elucidated, evidence suggests changes in the level of excitatory neurotransmission and neurotrophic factor signalling may be quite important. Read More

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Effects of the GluN2B-selective antagonist Ro 63-1908 on acquisition and expression of methamphetamine conditioned place preference in male and female rats.

Drug Alcohol Depend 2021 May 26;225:108785. Epub 2021 May 26.

Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.

Background: Methamphetamine abuse has increased significantly in recent years. Currently, there are no FDA-approved pharmacotherapies for the treatment of methamphetamine use disorder. The goal of the current study was to determine if the N-methyl-d-aspartate (NMDA) GluN2B-selective antagonist Ro 63-1908 can block the conditioned rewarding effects of methamphetamine as assessed in conditioned place preference (CPP). Read More

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Gamma-Decanolactone Alters the Expression of GluN2B, A Receptors, and COX-2 and Reduces DNA Damage in the PTZ-Induced Seizure Model After Subchronic Treatment in Mice.

Neurochem Res 2021 May 21. Epub 2021 May 21.

Laboratory of Neuropharmacology and Preclinical Toxicology, Health Basic Sciences Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

Gamma-decanolactone (GD) has been shown to reduce epileptic behavior in different models, inflammatory decreasing, oxidative stress, and genotoxic parameters. This study assessed the GD effect on the pentylenetetrazole (PTZ) model after acute and subchronic treatment. We evaluated the expression of the inflammatory marker cyclooxygenase-2 (COX-2), GluN2B, a subunit of the NMDA glutamate receptor, adenosine A1 receptor, and GD genotoxicity and mutagenicity. Read More

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Developmental up-regulation of NMDA receptors in the prefrontal cortex and hippocampus of mGlu5 receptor knock-out mice.

Mol Brain 2021 May 7;14(1):77. Epub 2021 May 7.

IRCCS Neuromed, Pozzilli, IS, Italy.

mGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5 mice and wild-type littermates at three developmental time points (PND9, - 21, and - 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5 mice at PND21. Read More

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Alcohol hangover induces nitric oxide metabolism changes by impairing NMDA receptor-PSD95-nNOS pathway.

Nitric Oxide 2021 May 5;113-114:39-49. Epub 2021 May 5.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL) Buenos Aires, Argentina. Electronic address:

Alcohol hangover is defined as the combination of mental and physical symptoms experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration approaches zero. We previously evidenced increments in free radical generation and an imbalance in antioxidant defences in non-synaptic mitochondria and synaptosomes during hangover. It is widely known that acute alcohol exposure induces changes in nitric oxide (NO) production and blocks the binding of glutamate to NMDAR in central nervous system. Read More

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Studies of aging nonhuman primates illuminate the etiology of early-stage Alzheimer's-like neuropathology: An evolutionary perspective.

Am J Primatol 2021 May 7:e23254. Epub 2021 May 7.

Division of Neuropharmacology and Neurologic Diseases, Department of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.

Tau pathology in Alzheimer's disease (AD) preferentially afflicts the limbic and recently enlarged association cortices, causing a progression of mnemonic and cognitive deficits. Although genetic mouse models have helped reveal mechanisms underlying the rare, autosomal-dominant forms of AD, the etiology of the more common, sporadic form of AD remains unknown, and is challenging to study in mice due to their limited association cortex and lifespan. It is also difficult to study in human brains, as early-stage tau phosphorylation can degrade postmortem. Read More

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Upregulation of Glutamatergic Receptors in Hippocampus and Locomotor Hyperactivity in Aged Spontaneous Hypertensive Rat.

Cell Mol Neurobiol 2021 May 5. Epub 2021 May 5.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung, Taiwan.

Epidemiologic studies have indicated that chronic hypertension may facilitate the progression of abnormal behavior, such as emotional irritability, hyperactivity, and attention impairment. However, the mechanism of how chronic hypertension affects the brain and neuronal function remains unclear. In this study, 58-week-old male spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats were used. Read More

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CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation.

Nat Neurosci 2021 Jun 29;24(6):777-785. Epub 2021 Apr 29.

Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Read More

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Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period.

Biomolecules 2021 Apr 28;11(5). Epub 2021 Apr 28.

Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland.

Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1. Read More

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GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats.

Sheng Li Xue Bao 2021 Apr;73(2):223-232

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, China.

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Read More

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Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.

Front Neurosci 2021 9;15:644100. Epub 2021 Apr 9.

Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN, CONICET-UBA), Buenos Aires, Argentina.

-methyl-D-aspartate receptors are heterotetramers composed of two GluN1 obligatory subunits and two regulatory subunits. In cognitive-related brain structures, GluN2A and GluN2B are the most abundant regulatory subunits, and their expression is subjected to tight regulation. During development, GluN2B expression is characteristic of immature synapses, whereas GluN2A is present in mature ones. Read More

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Young DAPK1 knockout mice have altered presynaptic function.

J Neurophysiol 2021 May 21;125(5):1973-1981. Epub 2021 Apr 21.

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

The death-associated protein kinase 1 (DAPK1) has recently been shown to have a physiological function in long-term depression (LTD) of glutamatergic synapses: acute inhibition of DAPK1 blocked the LTD that is normally seen at the hippocampal CA1 synapse in young mice, and a pharmacogenetic combination approach showed that this specifically required DAPK1-mediated suppression of postsynaptic Ca/calmodulin-dependent protein kinase II binding to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B during LTD stimuli. Surprisingly, we found here that genetic deletion of DAPK1 (in DAPK1 mice) did not reduce LTD. Paired pulse facilitation experiments indicated a presynaptic compensation mechanism: in contrast to wild-type mice, LTD stimuli in DAPK1 mice decreased presynaptic release probability. Read More

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Chronic Blockade of NMDAR Subunit 2A in the Hypothalamic Paraventricular Nucleus Alleviates Hypertension through Suppression of MEK/ERK/CREB Pathway.

Am J Hypertens 2021 Apr 15. Epub 2021 Apr 15.

Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an, China.

Background: N-methyl-D-aspartate Receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) plays critical roles in regulating sympathetic outflow. Studies showed that acute application of the antagonists of NMDAR or its subunits would reduce sympathetic nerve discharges. However, little is known about the effect of long-term management of NMDAR in hypertensive animals. Read More

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Maternal high-sugar diet results in NMDA receptors abnormalities and cognitive impairment in rat offspring.

FASEB J 2021 May;35(5):e21547

Department of Toxicology, Jagiellonian University Medical College, Kraków, Poland.

Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Read More

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Changes in concentrations of NMDA receptor subunit GluN2B, Arc and syntaxin-1 in dorsal hippocampus Schaffer collateral synapses in a rat learned helplessness model of depression.

J Comp Neurol 2021 Apr 12. Epub 2021 Apr 12.

Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Major depressive disorder involves changes in synaptic structure and function, but the molecular underpinnings of these changes are still not established. In an initial pilot experiment, whole-brain synaptosome screening with quantitative western blotting was performed to identify synaptic proteins that may show concentration changes in a congenital rat learned helplessness model of depression. We found that the N-methyl-d-aspartate receptor (NMDAR) subunits GluN2A/GluN2B, activity-regulated cytoskeleton-associated protein (Arc) and syntaxin-1 showed significant concentration differences between congenitally learned helpless (LH) and nonlearned helpless (NLH) rats. Read More

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Dysregulation of Ambient Glutamate and Glutamate Receptors in Epilepsy: An Astrocytic Perspective.

Front Neurol 2021 22;12:652159. Epub 2021 Mar 22.

Glial Biology in Health, Disease, and Cancer Center, Fralin Biomedical Research Institute, Virginia Tech Carilion, Roanoke, VA, United States.

Given the important functions that glutamate serves in excitatory neurotransmission, understanding the regulation of glutamate in physiological and pathological states is critical to devising novel therapies to treat epilepsy. Exclusive expression of pyruvate carboxylase and glutamine synthetase in astrocytes positions astrocytes as essential regulators of glutamate in the central nervous system (CNS). Additionally, astrocytes can significantly alter the volume of the extracellular space (ECS) in the CNS due to their expression of the bi-directional water channel, aquaporin-4, which are enriched at perivascular endfeet. Read More

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Protein-protein interactions at the NMDA receptor complex: From synaptic retention to synaptonuclear protein messengers.

Neuropharmacology 2021 06 2;190:108551. Epub 2021 Apr 2.

Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy. Electronic address:

N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that support essential functions throughout the brain. NMDARs are tetramers composed of the GluN1 subunit in complex with GluN2- and GluN3-type regulatory subunits, resulting in the formation of various receptor subtypes throughout the central nervous system (CNS), characterised by different kinetics, biophysical and pharmacological properties, and the abilities to interact with specific partners at dendritic spines. NMDARs are expressed at high levels, are widely distributed throughout the brain, and are involved in several physiological and pathological conditions. Read More

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Anticonvulsant Action of GluN2A-Preferring Antagonist PEAQX in Developing Rats.

Pharmaceutics 2021 Mar 19;13(3). Epub 2021 Mar 19.

Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, 14220 Prague, Czech Republic.

The GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors becomes dominant during postnatal development, overgrowing the originally dominant GluN2B subunit. The aim of our study was to show changes of anticonvulsant action of the GluN2A subunit-preferring antagonist during postnatal development of rats. Possible anticonvulsant action of GluN2A-preferring antagonist of NMDA receptors P = [[[(1S)-1-(4-bromophenyl)ethyl]amino](1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]phosphonic acid tetrasodium salt (PEAQX) (5, 10, 20 mg/kg s. Read More

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Early and Delayed Impact of Nanosilver on the Glutamatergic NMDA Receptor Complex in Immature Rat Brain.

Int J Mol Sci 2021 Mar 17;22(6). Epub 2021 Mar 17.

Laboratory of Pathoneurochemistry, Department of Neurochemistr, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.

Silver nanoparticles (AgNPs) are the one of the most extensively used nanomaterials. The strong antimicrobial properties of AgNPs have led to their use in a wide range of medical and consumer products. Although the neurotoxicity of AgNPs has been confirmed, the molecular mechanisms have not been extensively studied, particularly in immature organisms. Read More

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Wnt5a promotes hippocampal postsynaptic development and GluN2B-induced expression via the eIF2α HRI kinase.

Sci Rep 2021 Apr 1;11(1):7395. Epub 2021 Apr 1.

Centro de Envejecimiento y Regeneración (CARE UC), CARE UC Biomedical Center, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Av. Alameda 340, 8331150, Santiago, Chile.

Wnt signaling plays a key role in neurodevelopment and neuronal maturation. Specifically, Wnt5a stimulates postsynaptic assemblies, increases glutamatergic neurotransmission and, through calcium signaling, generates nitric oxide (NO). Trying to unveil the molecular pathway triggering these postsynaptic effects, we found that Wnt5a treatment induces a time-dependent increases in the length of the postsynaptic density (PSD), elicits novel synaptic contacts and facilitates F-actin flow both in in vitro and ex vivo models. Read More

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Specific pathogenic mutations in the M3 domain of the GluN1 subunit regulate the surface delivery and pharmacological sensitivity of NMDA receptors.

Neuropharmacology 2021 05 25;189:108528. Epub 2021 Mar 25.

Department of Neurochemistry, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic. Electronic address:

N-methyl-d-aspartate receptors (NMDARs) play an essential role in regulating glutamatergic neurotransmission. Recently, pathogenic missense mutations were identified in genes encoding NMDAR subunits; however, their effect on NMDAR activity is often poorly understood. Here, we examined whether three previously identified pathogenic mutations (M641I, A645S, and Y647S) in the M3 domain of the GluN1 subunit affect the receptor's surface delivery, agonist sensitivity, Mg block, and/or inhibition by the FDA-approved NMDAR blocker memantine. Read More

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Metaplastic Effects of Ketamine and MK-801 on Glutamate Receptors Expression in Rat Medial Prefrontal Cortex and Hippocampus.

Mol Neurobiol 2021 Mar 15. Epub 2021 Mar 15.

Neuropsychopharmacology Lab, Section Pharmacology, Department Diagnostic & Public Health, University of Verona, Policlinico GB Rossi, P.le Scuro 10, 37134, Verona, Italy.

Ketamine and MK-801 by blocking NMDA receptors may induce reinforcing effects as well as schizophrenia-like symptoms. Recent results showed that ketamine can also effectively reverse depressive signs in patients' refractory to standard therapies. This evidence clearly points to the need of characterization of effects of these NMDARs antagonists on relevant brain areas for mood disorders. Read More

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Icaritin Alleviates Glutamate-Induced Neuronal Damage by Inactivating GluN2B-Containing NMDARs Through the ERK/DAPK1 Pathway.

Front Neurosci 2021 22;15:525615. Epub 2021 Feb 22.

Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, China.

Excitatory toxicity due to excessive glutamate release is considered the core pathophysiological mechanism of cerebral ischemia. It is primarily mediated by N-methyl-D-aspartate receptors (NMDARs) on neuronal membranes. Our previous studies have found that icaritin (ICT) exhibits neuroprotective effects against cerebral ischemia in rats, but the underlying mechanism is unclear. Read More

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February 2021

GluN2B/N-methyl-D-aspartate receptor antagonists: Advances in design, synthesis, and pharmacological evaluation studies.

CNS Neurol Disord Drug Targets 2021 Mar 9. Epub 2021 Mar 9.

Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur Dist: Dhule (MS) 425405 . India.

Selective GluN2B/N-methyl-D-aspartate receptor (NMDAR) antagonists have exposed their clinical effectiveness in cluster of neurodegenerative diseases such as Epilepsy, Alzheimer's disease, Parkinson's disease, pain and depression. Hence, GluN2B/NMDAR is considered to be a prospective target for the management of neurodegenerative diseases. Here, we have discussed current results and significance of subunit selective GluN2B/NMDAR antagonists to pave the way for establishment of new, safe, and economical drug candidate in a near future. Read More

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Deconstruction - Reconstruction: Analysis of the Crucial Structural Elements of GluN2B-Selective, Negative Allosteric NMDA Receptor Modulators with 3-Benzazepine Scaffold.

Cell Physiol Biochem 2021 Mar;55(S3):1-13

GRK 2515, Chemical biology of ion channels (Chembion), Westfälische Wilhelms-Universität Münster, Münster, Germany,

Background/aims: The NMDA receptor plays a key role in the pathogenesis of neurodegenerative disorders including Alzheimer's and Huntington's disease, as well as depression and drug or alcohol dependence. Due to its participation in these pathologies, the development of selective modulators for this ion channel is a promising strategy for rational drug therapy. The prototypical negative allosteric modulator ifenprodil inhibits selectively GluN2B subunit containing NMDA receptors. Read More

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Suppression of food restriction-evoked hyperactivity in activity-based anorexia animal model through glutamate transporters GLT-1 at excitatory synapses in the hippocampus.

Synapse 2021 Jul 16;75(7):e22197. Epub 2021 Mar 16.

The Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA.

Severe voluntary food restriction is the defining symptom of anorexia nervosa (AN), but anxiety and excessive exercise are maladaptive symptoms that contribute significantly to the severity of AN and which individuals with AN have difficulty suppressing. We hypothesized that the excitability of hippocampal pyramidal neurons, known to contribute to anxiety, leads to the maladaptive behavior of excessive exercise. Conversely, since glutamate transporter GLT-1 dampens the excitability of hippocampal pyramidal neurons through the uptake of ambient glutamate and suppression of the GluN2B-subunit containing NMDA receptors (GluN2B-NMDARs), GLT-1 may contribute toward dampening excessive exercise. Read More

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Exo70 intracellular redistribution after repeated mild traumatic brain injury.

Biol Res 2021 Feb 16;54(1). Epub 2021 Feb 16.

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O´Higgins 340, Santiago, Chile.

Background: Exo70 is a subunit of the greater exocyst complex, a collection of proteins that oversees cellular membrane addition and polarized exocytosis by acting as a tethering intermediate between the plasma membrane and newly synthesized secretory vesicles. Although Exo70 function has been implicated in several developmental events including cytokinesis and the establishment of cell polarity, its role in neuropathologies is poorly understood. On the other hand, traumatic brain injury is the result of mechanical external force including contusion, fast acceleration, and expansive waves that produce temporal or permanent cognitive damage and triggers physical and psychosocial alterations including headache, memory problems, attention deficits, difficulty thinking, mood swings, and frustration. Read More

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February 2021

Secretagogin marks amygdaloid PKCδ interneurons and modulates NMDA receptor availability.

Proc Natl Acad Sci U S A 2021 Feb;118(7)

SE-NAP Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, H-1094 Budapest, Hungary;

The perception of and response to danger is critical for an individual's survival and is encoded by subcortical neurocircuits. The amygdaloid complex is the primary neuronal site that initiates bodily reactions upon external threat with local-circuit interneurons scaling output to effector pathways. Here, we categorize central amygdala neurons that express secretagogin (Scgn), a Ca-sensor protein, as a subset of protein kinase Cδ (PKCδ) interneurons, likely "off cells. Read More

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February 2021

Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity.

J Neurosci 2021 03 1;41(10):2119-2134. Epub 2021 Feb 1.

Institute of Physiology CAS, Prague 4, 142 20, Czech Republic

NMDARs are ligand-gated ion channels that cause an influx of Na and Ca into postsynaptic neurons. The resulting intracellular Ca transient triggers synaptic plasticity. When prolonged, it may induce excitotoxicity, but it may also activate negative feedback to control the activity of NMDARs. Read More

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