ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The ability of BDNF to modify neurogenesis and depressive-like behaviors is dependent upon phosphorylation of tyrosine residues 365/367 in the GABA(A)-receptor γ2 subunit.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Dentate Gyrus ERK1/2-BDNF Signaling is Required for the Antidepressant Effect of Microglial Stimulation in a Male Mouse Model of Depression Induced by Adolescent Nicotine Exposure.Neurochemical research · 2026Article
- Functional and evolutionary characteristics of human genes encoding cell surface receptors involved in the regulation of appetite.Journal of integrative bioinformatics · 2025Article
- Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors.Molecules (Basel, Switzerland) · 2022Article
- Article
- Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine.Metabolic brain disease · 2021Article
- Structural basis of GABARAP-mediated GABANature communications · 2021Article
- Regulation of GABAInternational journal of molecular sciences · 2020Review
- Recovery of High Interference Memory in Spite of Lingering Cognitive Deficits in a Longitudinal Pilot Study of Hospitalized Depressed Patients.Frontiers in psychiatry · 2020Article
- Pioglitazone treatment prior to transplantation improves the efficacy of human mesenchymal stem cells after traumatic brain injury in rats.Scientific reports · 2019Article
- Pulsed electromagnetic field attenuated PTSD-induced failure of conditioned fear extinction.Iranian journal of basic medical sciences · 2019Article
- Induced pluripotent stem cells for neural drug discovery.Drug discovery today · 2019Review
- Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions.Frontiers in cellular neuroscience · 2019Review
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- γ2 GABAFrontiers in cellular neuroscience · 2018Review
- Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood.Scientific reports · 2017Article
- 3,5,6,7,8,3',4'-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation.International journal of molecular sciences · 2017Article
- Pluripotent stem cells in neuropsychiatric disorders.Molecular psychiatry · 2017Review
- Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.Molecular neurobiology · 2017Review
- Prefrontal Cortex GABAergic Deficits and Circuit Dysfunction in the Pathophysiology and Treatment of Chronic Stress and Depression.Current opinion in behavioral sciences · 2017Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal activity, neurogenesis, and depressive-like behaviors; however, downstream effectors by which BDNF exerts these varying actions remain to be determined. Here we reveal that BDNF induces long-lasting enhancements in the efficacy of synaptic inhibition by stabilizing γ2 subunit-containing GABA(A) receptors (GABA(A)Rs) at the cell surface, leading to persistent reductions in neuronal excitability. This effect is dependent upon enhanced phosphorylation of tyrosines 365 and 367 (Y365/7) in the GABA(A)R γ2 subunit as revealed using mice in which these residues have been mutated to phenyalanines (Y365/7F). Heterozygotes for this mutation exhibit an antidepressant-like phenotype, as shown using behavioral-despair models of depression. In addition, heterozygous Y365/7F mice show increased levels of hippocampal neurogenesis, which has been strongly connected with antidepressant action. Both the antidepressant phenotype and the increased neurogenesis seen in these mice are insensitive to further modulation by BDNF, which produces robust antidepressant-like activity and neurogenesis in wild-type mice. Collectively, our results suggest a critical role for GABA(A)R γ2 subunit Y365/7 phosphorylation and function in regulating the effects of BDNF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.