ArticleAlzheimer's research & therapy2021
Reversible GABAergic dysfunction involved in hippocampal hyperactivity predicts early-stage Alzheimer disease in a mouse model.
Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Co-activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring Linalool-Based Phytotherapy for Excitatory/Inhibitory Imbalance in Alzheimer's Disease: A Review of Lavender and Cannabis Therapeutic Effects on Sleep, Seizures, and Cognition.Phytotherapy research : PTR · 2026Review
- Poly(lactic-co-glycolic acid) immunomodulatory nanoparticles attenuate neuroinflammation and Alzheimer's disease-related pathology in 5xFAD mice.bioRxiv : the preprint server for biology · 2026Article
- Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026Review
- Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease in vivo.Communications biology · 2026Article
- Functional-Structural Coupling: Brain Reorganization in Presbycusis Is Related to Cognitive Impairment.eNeuro · 2026Article
- An Acebuche Oil-Enriched Diet Prevents Early-Stage Cerebrovascular Alterations in the 5xFAD Mouse Model of Alzheimer's Disease.Nutrients · 2026Article
- Introducing the SAGE study: a multimodal protocol for testing a GABAergic mechanism of age-related episodic memory impairment across the sexes.BMJ neurology open · 2026Article
- Glucose metabolism alterations and Aβ deposition in AD and FTD are related to the distribution of neurotransmitter systems.European journal of nuclear medicine and molecular imaging · 2026Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Neuronal and Glial α7 Nicotinic Acetylcholine Receptors: Role in Alzheimer's Disease Pathophysiology.Life (Basel, Switzerland) · 2025Review
- Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.Cell & bioscience · 2025Article
- GABA transporter 1 is a promising drug target for CUL4B mutation-associated epilepsy.Acta pharmacologica Sinica · 2025Article
- The impact of GABA and GABAergic pathway in polycystic ovary syndrome: a systematic review.Obstetrics & gynecology science · 2025Article
- HCN2 deficiency correlates with memory deficits and hyperexcitability of dCA1 pyramidal neurons in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.Molecular neurobiology · 2025Review
- The X-linked intellectual disability gene CUL4B is critical for memory and synaptic function.Acta neuropathologica communications · 2024Article
- A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Regulation of Hippocamposeptal Synaptic Transmission by GABAJournal of molecular neuroscience : MN · 2024Article
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown.
methodsHere, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Biochemical methods, electron microscopic imaging, behavioral tests, and intraventricular drug delivery applied with osmotic pumps were used in this study.
resultsWe confirmed hyperactivity of hippocampal CA1 pyramidal neurons in 5XFAD mice using whole-cell electrophysiological recording at 2.5 months old, when local Aβ-positive plaques had not developed and only mild cognitive dysfunction occurred. We further discovered attenuated inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents in CA1 pyramidal neurons, in which the intrinsic excitability was unchanged. Moreover, the density of both γ-aminobutyric acid A (GABA
conclusionsInhibitory postsynaptic disruption critically contributes to abnormalities in the hippocampal network and cognition in 5XFAD mice and possibly in AD. Therefore, strengthening the GABAergic system could be a promising therapy for AD in the early stages.
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