ArticleAlzheimer's research & therapy2025
Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Hilar mossy cells control structural and functional organization in the dentate gyrus.bioRxiv : the preprint server for biology · 2026Article
- Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026Review
- Selective impairment of long-term depression in accumbal D1-MSNs involves calcium-permeable AMPARs in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Amyloid-β acute exposition affects the CA1 hippocampal network activity and its topological organization, evaluated with multielectrode arrays.Frontiers in dementia · 2026Article
- Towards an Understanding of the Dentate Gyrus Hilus.Hippocampus · 2025Review
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Abstract
backgroundHyperexcitability in Alzheimer's disease (AD) is proposed to emerge early and contribute to disease progression. The dentate gyrus (DG) and its primary cell type, granule cells (GCs) are implicated in hyperexcitability in AD. Hence, we hypothesized that mossy cells (MCs), important regulators of GC excitability, contribute to early hyperexcitability in AD. Indeed, MCs and GCs are linked to hyperexcitability in epilepsy.
methodsUsing the Tg2576 model of AD and WT mice (~ 1 month-old), we compared MCs and GCs electrophysiologically and morphologically, assessed the activity marker c-Fos, Aβ expression and a hippocampal- and MC-dependent memory task that is impaired at 3-4 months of age in Tg2576 mice.
resultsTg2576 MCs had increased spontaneous excitatory events (sEPSP/Cs) and decreased spontaneous inhibitory currents (sIPSCs), increasing the excitation/inhibition ratio. Additionally, Tg2576 MC intrinsic excitability was enhanced. Consistent with in vitro results, Tg2576 MCs showed enhanced c-Fos protein expression. Tg2576 MCs had increased intracellular Aβ expression, suggesting a reason for increased excitability. GCs showed increased excitatory and inhibitory input without changes in intrinsic properties, consistent with effects of increased MC activity. In support, increased GC activity was normalized by an antagonist of MC input to GCs. Also in support, Tg2576 MC axons showed sprouting to the area of GC dendrites. These effects occurred before an impairment in the memory task, suggesting they are extremely early alterations.
conclusionsAlterations in Tg2576 MCs and GCs early in life suggest an early role for MCs in increased GC excitability. MCs may be a novel target to intervene in AD pathophysiology at early stages.
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