ArticleEpilepsy research2015
Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility.
Article in Epilepsy research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 120 citations in OpenAlex.
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- A depression-like phenotype is associated with discrete defects in the primary hippocampal circuit.Translational psychiatry · 2026Article
- The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice.Behavioral and brain functions : BBF · 2026Article
- Excitability-margin narrowing as a candidate gating mechanism for maladaptive circuit reactivation: a ventral CA1-centered model.Frontiers in behavioral neuroscience · 2026Article
- Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.Molecular psychiatry · 2025Article
- Midbrain KCC2 downregulation: Implications for stress-related and substance use behaviors.Current opinion in neurobiology · 2024Review
- Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome.EMBO molecular medicine · 2024Article
- Simple synaptic modulations implement diverse novelty computations.Cell reports · 2024Article
- Simple synaptic modulations implement diverse novelty computations.bioRxiv : the preprint server for biology · 2024Article
- Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration.Journal of clinical medicine · 2024Article
- Heterogeneous subpopulations of GABAiScience · 2024Article
- Bidirectional Regulation of GABALife (Basel, Switzerland) · 2024Review
- Influence of early-life stress on hippocampal synaptic and network properties.Frontiers in neural circuits · 2024Review
- Early establishment of chloride homeostasis in CRH neurons is altered by prenatal stress leading to fetal HPA axis dysregulation.Frontiers in molecular neuroscience · 2024Article
- Therapeutic potential for KCC2-targeted neurological diseases.The Japanese dental science review · 2023Review
- Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: role of inflammatory response and oxidative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Habenula as a Possible Target for Treatment-Resistant Depression Phenotype in Wistar Kyoto Rats.Molecular neurobiology · 2023Article
- Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The most commonly reported precipitating factor for seizures is stress. However, the underlying mechanisms whereby stress triggers seizures are not yet fully understood. Here we demonstrate a potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA (EGABA) associated with a dephosphorylation of the potassium chloride co-transporter, KCC2. Mice subjected to chronic restraint stress (30min/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20mg/kg). Following chronic stress, but not acute stress, we observe a dephosphorylation of KCC2 residue S940, which regulates KCC2 cell surface expression and function, in the hippocampus. To determine the impact of alterations in KCC2 expression following chronic stress, we performed gramicidin perforated patch recordings to measure changes in EGABA and neuronal excitability of principal hippocampal neurons. We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress. In addition, there is an increase in the intrinsic excitability of CA1 pyramidal neurons, evident by a shift in the input-output curve which could be reversed with the NKCC1 inhibitor, bumetanide. These data uncover a potential mechanism involving chronic stress-induced plasticity in chloride homeostasis which may contribute to stress-induced seizure susceptibility.
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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.