ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Modulation of GABAA receptor signaling increases neurogenesis and suppresses anxiety through NFATc4.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
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- Deregulation of NF-κB associated long non-coding RNAs in bipolar disorder.Metabolic brain disease · 2023Article
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- Adolescent anxiety and pain problems: A joint, genome-wide investigation and pathway-based analysis.PloS one · 2023Article
- The CaNeuropharmacology · 2022Article
- The feedback loop between calcineurin, calmodulin-dependent protein kinase II, and nuclear factor of activated T-cells regulates the number of GABAergic neurons during planarian head regeneration.Frontiers in molecular neuroscience · 2022Article
- Regulation of GABAMembranes · 2021Review
- Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through CaFrontiers in cell and developmental biology · 2021Article
- Epigenetic Modifications of GABAergic Interneurons Contribute to Deficits in Adult Hippocampus Neurogenesis and Depression-Like Behavior in Prenatally Stressed Mice.The international journal of neuropsychopharmacology · 2020Article
- Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2020Article
- Elevated Level of PKMζ Underlies the Excessive Anxiety in an Autism Model.Frontiers in molecular neuroscience · 2019Article
- Postacute Delivery of GABAStroke · 2018Article
- Neural mechanisms underlying GABAergic regulation of adult hippocampal neurogenesis.Cell and tissue research · 2018Review
- Palmitoylation as a Functional Regulator of Neurotransmitter Receptors.Neural plasticity · 2018Review
- Pumilio2-deficient mice show a predisposition for epilepsy.Disease models & mechanisms · 2017Article
- Neurotransmitter-Regulated Regeneration in the Zebrafish Retina.Stem cell reports · 2017Article
- Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Correlative evidence suggests that GABAergic signaling plays an important role in the regulation of activity-dependent hippocampal neurogenesis and emotional behavior in adult mice. However, whether these are causally linked at the molecular level remains elusive. Nuclear factor of activated T cell (NFAT) proteins are activity-dependent transcription factors that respond to environmental stimuli in different cell types, including hippocampal newborn neurons. Here, we identify NFATc4 as a key activity-dependent transcriptional regulator of GABA signaling in hippocampal progenitor cells via an unbiased high-throughput genome-wide study. Next, we demonstrate that GABAA receptor (GABAAR) signaling modulates hippocampal neurogenesis through NFATc4 activity, which in turn regulates GABRA2 and GABRA4 subunit expression via binding to specific promoter responsive elements, as assessed by ChIP and luciferase assays. Furthermore, we show that selective pharmacological enhancement of GABAAR activity promotes hippocampal neurogenesis via the calcineurin/NFATc4 axis. Importantly, the NFATc4-dependent increase in hippocampal neurogenesis after GABAAR stimulation is required for the suppression of the anxiety response in mice. Together, these data provide a novel molecular insight into the regulation of the anxiety response in mice, suggesting that the GABAAR/NFATc4 axis is a druggable target for the therapy of emotional disorders.
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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 OpenQuestion graph.