Ask about this productRelated genes to: GABRA1 antibody
- Gene:
- GABRA1 NIH gene
- Name:
- gamma-aminobutyric acid type A receptor alpha1 subunit
- Previous symbol:
- -
- Synonyms:
- EJM5
- Chromosome:
- 5q34
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-02
- Date modifiied:
- 2016-02-04
Related products to: GABRA1 antibody
Related articles to: GABRA1 antibody
- Conventional tribromoethanol anesthesia is compromised by solvent-related toxicity, limiting its utility in prolonged experimental protocols. We hypothesized that reformulation with 1,2-propanediol could improve its biosafety while revealing its potential mechanism of action in the central nervous system. - Source: PubMed
Publication date: 2026/08/17
Li XiaChen YanmingXiao XinyiXu Guoheng - Disease variants in genes encoding γ-aminobutyric acid type A receptor (GABAR) subunits are major causes of developmental and epileptic encephalopathies (DEEs). There is no effective treatment for these DEEs, although the GABAR is a major target for antiseizure drugs. We previously identified the therapeutic effect of 4-phenylbutyrate (PBA) in knockin DEE mice and in this study tested the effect of the drug in variants that encode the α1 subunit of GABAR. We used a multidisciplinary approach including in silico structural modeling, flow cytometry, patch-clamp recordings and biochemistry in conjunction with differential tagging of the wildtype (WT) and the mutant alleles to evaluate the effect of PBA on rescue of GABAR subunit expression, surface trafficking, and function in vitro in a heterologous HEK293T cell model and in vivo in mice. We found that the α1 subunit expression at both the total level and the cell surface was reduced when the variant α1 protein was present, suggesting reduced functional receptor availability on the cell membrane and synapse. Patch-clamp recordings identified that α1 variants reduced GABA-evoked current amplitude. In silico prediction indicated reduced protein stability for variants by negative ∆∆G values. PBA increased both total and surface expression of WT α1 and α1 variants and improved expression of both WT and variant α1 alleles when these were co-expressed. Importantly, PBA also increased the GABAR expression in the cortex and thalamus of the mice. This study indicates that PBA is a promising treatment option for DEEs associated with mutations. Our previous work has demonstrated that PBA improves proteostasis by enhancing expression of the WT allele, repairing the mutant allele, and reducing endoplasmic reticulum stress in other DEEs associated with and mutations. Importantly, it can mitigate seizures and improve neurobehavioral phenotypes at behavioral levels. Based on this and our previous work on and mutations, we propose that PBA holds promise as a common medicine for multiple genetic neurologic disorders that share the proteostasis pathology with a broad clinical application in DEEs. - Source: PubMed
Publication date: 2026/07/24
Song Ziang DebbieZavalin KirillShen WangzhenDeLeeuw Melissa BHunn Genevieve XEda Ria SMa LiWang JuexinKang Jing-Qiong - Depression is characterized by a dysregulated brain-gut axis. Xiaoyao San (XYS), a classic Traditional Chinese Medicine formula for soothing Liver and strengthening Spleen, is clinically effective in alleviating depression. However, the systems-level mechanisms by which XYS coordinates gut-brain communication to exert its antidepressant effects remain insufficiently understood. This study aimed to systematically elucidate the antidepressant mechanisms of XYS, with a focus on identifying a key gut-derived metabolic pathway that modulates prefrontal cortex (PFC) function. A mouse model of depression was established using isolated housing combined with chronic unpredictable mild stress (CUMS). Mice were treated with XYS at low, medium, and high doses or paroxetine. We employed a multimodal approach, integrating behavioral tests, resting-state functional magnetic resonance imaging (rs-fMRI), gut microbiota profiling (16S rRNA sequencing), serum metabolomics and PFC transcriptomics. To establish causal evidence, pseudo-germ-free mice received fecal microbiota transplantation (FMT) from donor mice treated with XYS, followed by comprehensive behavioral and biochemical assessments. XYS treatment significantly ameliorated depressive-like behaviors and restored functional connectivity within emotion-regulation brain networks. Multi-omics integration revealed that XYS reshaped the gut microbiota, which was associated with a reduction in systemic levels of kynurenine (KYN), a key tryptophan-derived metabolite. In the PFC, this decrease in KYN was accompanied by the normalization of aryl hydrocarbon receptor (AhR) signaling activity. Furthermore, GABAergic neurotransmission, mediated by γ-aminobutyric acid (GABA), was enhanced, as evidenced by upregulated expression of glutamate decarboxylase 1 (Gad1), gamma-aminobutyric acid type A receptor subunit alpha1 (Gabra1), increased GABA content, and elevated levels of key synaptic plasticity-related molecules, including brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and synaptophysin (SYN). Critically, FMT from XYS-treated donors recapitulated the antidepressant phenotype in recipient mice, directly implicating the gut microbiota in these therapeutic effects. This study demonstrates that XYS alleviates depression by orchestrating a gut-brain signaling cascade that converges on the PFC to enhance inhibitory synaptic transmission. These findings provide novel and causal mechanistic insights into the brain-gut modulatory action of XYS, offering a comprehensive framework for its therapeutic potential in treating depression. - Source: PubMed
Publication date: 2026/08/08
Chen QingLi SiyingFu ShanshanMo ChanHuang ShaWang YuhuaLi LanGao TingtingKuang ShanshanZheng RuiseWen JinjieLv Zhiping - Isopropoxate (IPPO), an emerging imidazole ester-type new psychoactive substance, poses potential risks to public health and the environment, yet its neurotoxic mechanisms remain poorly understood. In this study, 8-week-old C57BL/6 J mice were used to evaluate the effects of IPPO on the blood-brain barrier (BBB), oxidative stress, neuroinflammation, and neurotransmitter receptor systems through UPLC-MS/MS-based tissue distribution analysis, quantitative real-time PCR, TUNEL staining, and molecular docking. At a dose of 3 mg/kg, IPPO accumulated in brain tissue and induced cerebral edema. Marked reductions in the tight-junction proteins Occludin and Claudin-5, together with decreased expression of the efflux transporter genes Abcb1a and Abcb1b, indicated impairment of blood-brain barrier (BBB) integrity. In brain tissue, malondialdehyde (MDA) increased by approximately 30%, catalase (CAT) activity decreased by approximately 20%, and glutathione (GSH) content declined by approximately 8%, demonstrating enhanced lipid peroxidation (LPO) and weakened antioxidant defenses. IPPO exposure also upregulated components of the NLRP3 inflammasome and the pro-inflammatory mediators IL-1β, IL-6, and TNF, while reducing the anti-inflammatory cytokine IL-10 by approximately 26%, indicating disruption of the pro-/anti-inflammatory balance. Within neurotransmitter systems, DRD1 and GABRA1 protein levels increased, Taar1 expression decreased, and the immediate-early genes Fos and Arc were markedly upregulated, consistent with dysregulation of dopaminergic, GABAergic, and neuronal activity-related signaling. Molecular docking further indicated stable interactions of IPPO with GABA and DRD1 receptors, supporting a potential direct influence on neurotransmission through key receptor targets. Transcriptomic profiling corroborated suppression of tight-junction-related genes and disturbance of neurotransmitter-associated pathways. Collectively, these findings identify a coordinated neurotoxic mechanism in which IPPO disrupts the BBB, promotes oxidative stress and neuroinflammation, and alters neurotransmitter receptor signaling. - Source: PubMed
Publication date: 2026/08/08
Cao RenjuanChen ZienCai JihongMei PengfeiLiu XinRen YuanLiu Chao - Missense variants in genes encoding GABA receptors are involved in the pathophysiology of common and rare epilepsies. Variant effects on channel biophysical function are associated with key clinical characteristics and treatment response. Predicting variant effects is therefore key to improving care for individuals with GABA receptor-related disorders. - Source: PubMed
Publication date: 2026/08/03
Boßelmann Christian MOrtiz SebastianDahl RebekkaLiao Vivian W YEl-Kamand SereneLin Susan X NHon Kan Anthony SzeBrünger TobiasLal DennisLerche HolgerKreuer JulesPfeifer NicoChebib MaryAbsalom Nathan LAhring Philip KMøller Rikke S