Ask about this productRelated genes to: GRIN2A Blocking Peptide
- Gene:
- GRIN2A NIH gene
- Name:
- glutamate ionotropic receptor NMDA type subunit 2A
- Previous symbol:
- NMDAR2A
- Synonyms:
- GluN2A
- Chromosome:
- 16p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-09-18
- Date modifiied:
- 2016-02-05
Related products to: GRIN2A Blocking Peptide
Related articles to: GRIN2A Blocking Peptide
- Adolescence is associated with the emergence of several psychiatric disorders including schizophrenia. Recent studies have identified both common and rare variants of the GRIN2A gene as risk factors for schizophrenia. GRIN2A encodes the GluN2A subunit of the NMDA receptor and is developmentally regulated with low cortical expression at birth that reaches adult levels in adolescence. While global knockouts of Grin2a produce abnormal behavior in mice, little is known about the functional consequences of manipulating this gene specifically in dopamine neurons, a cell type implicated in schizophrenia pathophysiology. We find that, unlike cortical regions where GluN2A levels remain stable throughout adolescence, GluN2A naturally declines in dopamine neuron-containing brain regions in this developmental period. This suggests that adolescent dopamine neurons may be especially vulnerable to further reductions of GluN2A caused by damaging GRIN2A variants. Consistent with this idea, we find that a genetically driven reduction of Grin2a in midbrain dopamine neurons of adolescent rats is sufficient to recapitulate behaviors that are consistent with some aspects of positive symptoms of schizophrenia. These include hypersensitivity to amphetamine, diminished effort optimization, impaired ability to use feedback to modify motivated actions, and disrupted dopamine release during prediction error signaling. Computational modeling of the behavioral data further revealed reduced capacity to gate associative processes based on previous learning. These data describe a novel role for GluN2A-containing dopamine neurons in prediction error signaling and provide a rodent model to explore how mutations in GRIN2A may contribute to the latent presentation of dopamine-related symptoms in schizophrenia. - Source: PubMed
Publication date: 2026/05/13
Kielhold Michelle LJacobs David STorrado Pacheco AlejandroLefner Merridee JBogachuk Alina PLebowitz Joseph JLangdon Angela JWilliams John TZweifel Larry SMoghaddam Bita - Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) represents a rare but severe group of childhood onset epilepsies characterized by sleep-potentiated epileptiform activity, seizures, and developmental stagnation or regression affecting cognition, language, and behavior. Once considered a self-limited electroencephalographic (EEG) phenomenon, D/EE-SWAS is now recognized as a disorder of brain network dysfunction in which persistent epileptiform discharges during non-rapid eye movement sleep disrupt synaptic plasticity, sleep-dependent memory consolidation, and neurodevelopmental trajectories. This review synthesizes recent advances in clinical phenotyping, genetics, neurophysiology, and therapeutics. Etiologically, D/EE-SWAS is highly heterogeneous, with pathogenic variants identified in nearly half of affected individuals, including copy number variants and single-gene disorders involving ion channels, synaptic proteins, and transcriptional regulators. GRIN2A is the most frequently implicated gene, although marked intrafamilial and interfamilial variability underscores the role of modifying genetic and network-level factors. Structural lesions-particularly those affecting thalamocortical circuits-represent another major disease substrate and are critical for treatment stratification. At the mechanistic level, abnormal thalamocortical oscillations, impaired sleep architecture, and disruption of slow-wave and spindle activity provide a pathophysiological framework linking EEG abnormalities to cognitive and behavioral deterioration. Neuroimaging and EEG-functional magnetic resonance imaging studies support a model of widespread network inhibition and disconnection extending beyond the primary epileptogenic zone. Therapeutically, corticosteroids currently represent the most effective first-line treatment, demonstrating superior cognitive outcomes compared with benzodiazepines, although relapse after tapering is common, and optimal dosing strategies remain undefined. Precision medicine approaches, including N-methyl-D-aspartate receptor-targeted therapies for GRIN variants and channel-specific treatments such as primidone for TRPM3 gain of function, offer promising avenues toward disease modification. Epilepsy surgery should be considered early in children with unilateral structural etiologies, where it can provide substantial neurodevelopmental benefit. Future priorities include standardized outcome measures, integration of sleep-based biomarkers, refinement of steroid protocols, and international collaborative trials to improve long-term neurodevelopmental outcomes in this vulnerable population. - Source: PubMed
Publication date: 2026/04/28
Specchio NicolaAuvin StéphaneBrunklaus AndreasDe Giorgis ValentinaDi Micco ValentinaGardella ElenaJansen Floor ENabbout RimaPepi ChiaraRubboli GuidoTrivisano MarinaCuratolo Paolo - Depression and anxiety during pregnancy are major public health concerns with lasting consequences for mother and child. Although the gut microbiome contributes to stress and mood regulation, its role in preconceptional stress and transgenerational outcomes remains unclear. Here, we examined behavioral, microbial, and thalamic transcriptional effects of preconceptional social isolation rearing (SIR) in female mice and tested whether maternal probiotic supplementation mitigates these alterations. SIR females displayed increased anxiety-like and social-avoidant behavior, reduced gut microbial diversity, depletion of Odoribacter, Tuzzerella, and Alloprevotella, and enrichment of Bacteroides and Lachnospiraceae. A multispecies probiotic (Lactobacillus rhamnosus HN001, L. acidophilus La-14, Bifidobacterium lactis HN019) reversed these behavioral and microbial changes. Adult offspring of SIR dams showed sex-dependent behavioral deficits and microbial alterations partly reflecting maternal patterns. Prenatal SIR was associated with reduced thalamic Bdnf expression in offspring and altered Grin2a/2b selectively in males. In contrast, prenatal probiotic exposure exerted broader transcriptional effects and restored Bdnf levels in SIR offspring. SIR-induced increases in Lachnospiraceae were transmitted to offspring, whereas reductions in Ruminococcaceae were normalized by maternal probiotic treatment. Predicted functional profiling indicated sex-dependent modulation of microbial pathways related to tryptophan and central carbon metabolism. These findings demonstrate enduring transgenerational effects of preconceptional stress on the gut-brain axis and support maternal probiotic supplementation as a potential strategy to mitigate stress-induced dysregulation. - Source: PubMed
Publication date: 2026/03/29
Iachizzi MonicaZajac NataliaRuiz José LuisGüller TanjaRabin RonSchalbetter Sinade Cillis FlorianaMoccia Maria DomenicaCattaneo AnnamariaCryan John FRichetto Juliet - Neurotoxicity induced by excessive glutamatergic signaling is associated with synaptic dysfunction, calcium imbalance, and oxidative stress, which are key molecular events implicated in several neurodegenerative conditions. Monosodium glutamate (MSG), a common flavor enhancer, may exert neurotoxic effects, particularly on synaptic integrity, though mechanisms remain unclear. Tannic acid (TA), a natural polyphenol, has been proposed as a neuroprotective compound. This study investigated the impact of MSG on synaptic components beyond classical AD markers and assessed the protective potential of TA. Rats were randomly divided into four groups (n = 6 per group) and treated with MSG (2 g/kg) and/or TA (50 mg/kg) by oral gavage for 21 consecutive days. Gene and protein expression levels of the synaptic markers (GRIN2A, GRIN2B, DLG2, SNAP25, SCN2A, and ATP2B2) in the cerebral cortex were analyzed using qPCR and western blot. MSG treatment significantly downregulated SNAP25, GRIN2B, DLG2, and SCN2A at both mRNA and protein levels, indicating synaptic dysfunction. GRIN2A and ATP2B2 showed reduced mRNA expression, but protein levels were inconsistent. MSG+TA group showed no significant difference compared with the control group, while TA alone produced minimal changes, suggesting that its role is primarily protective under toxic stress. These findings suggest that chronic MSG exposure disrupts synaptic molecular architecture, whereas the restorative effect of TA may be attributed to its ability to modulate MSG-induced molecular alterations. The data emphasize synaptic pathways as alternative neurotoxicity targets and highlight TA's potential in mitigating diet-related excitotoxic synaptic alterations. Further functional and pathway-based studies are needed to confirm the underlying mechanisms. - Source: PubMed
Publication date: 2026/03/27
Karagac Medine SibelKoçpinar Enver FehimCeylan Hamid - Intermittent theta burst stimulation (iTBS) is increasingly explored as a non-invasive neuromodulatory approach capable of inducing long-lasting plasticity with potential therapeutic value in age-related neurological and psychiatric conditions. However, the cellular and molecular mechanisms underlying iTBS protocols remain largely unknown, limiting its further therapeutic development. - Source: PubMed
Publication date: 2026/03/09
Popovic DanicaZaric Kontic MarinaZeljkovic Jovanovic MilicaMilosevic MilenaMartic TeodoraRadukic TamaraStekic AndjelaGlavonic EmilijaJakovljevic AnaMihajlovic KatarinaAdzic Bukvic MarijaStevanovic IvanaDragic Milorad