ArticleCell communication and signaling : CCS2024
Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Review
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- Deciphering the microenvironment of adult neurogenesis: a perspective from neurodegenerative diseases.Translational neurodegeneration · 2026Review
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Neuron-specific transcriptomic dysregulation in methotrexate-induced cognitive impairment revealed by SnRNA-seq.International journal of surgery (London, England) · 2026Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- α-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.Nutrition & metabolism · 2025Article
- The Inflammatory Axis of LncRNA Ftx/miR-382-5p/NRG1 in the Differential Diagnosis and Prognosis of Multiple Sclerosis and Neuromyelitis Optica.Inflammation · 2025Article
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.Epilepsy & behavior : E&B · 2025Article
- Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease.Biochemistry and biophysics reports · 2025Article
- Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model.Journal of neuroinflammation · 2025Article
- Astaxanthin Inhibits Ferroptosis of Hippocampal Neurons in Kainic Acid-Induced Epileptic Mice by Activating the Nrf2/GPX4 Signaling Pathway.CNS neuroscience & therapeutics · 2025Article
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.medRxiv : the preprint server for health sciences · 2025Article
- Altered GABAergic signaling and chloride homeostasis in eye movement circuits during late neurodevelopment: implications for Alzheimer's disease therapy.Frontiers in pharmacology · 2025Review
- Glymphatic System Dysfunction in Elderly Patients with Late-Onset Epilepsy and Comorbid Chronic Insomnia Revealed by Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS).Neuropsychiatric disease and treatment · 2025Article
- Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.Journal of clinical medicine · 2024Review
- Neurologists' approaches and challenges in managing early-stage Alzheimer's disease: A survey of clinical practices.Bioinformation · 2024Article
- Identification of early Alzheimer's disease subclass and signature genes based on PANoptosis genes.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPatients with Alzheimer's disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial.
methodsFour-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated.
resultsAPP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV
conclusionOur results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.
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