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This is a Experimental Study study.

September 26, 2025Journal of Alzheimer s Disease0 citations

Alterations in neuronal excitability and AMPA-mediated neurotransmission in an APP/PS1 neuronal culture model derived from nucleus accumbens

PSPaulina Saavedra IMI. Meza NRNicolás Riffo-Lepe

Key Points

Alterations in neuronal excitability occurred alongside increased AMPAergic synaptic currents in APP/PS1 neurons at 15 days in vitro.
APP/PS1 neurons exhibited higher intracellular accumulation of Aβ at 10 and 15 days in vitro, linking Aβ build-up to synaptic dysfunction.
The study utilized a neuronal culture model to explore changes in excitability and neurotransmission in the context of Alzheimer's disease.
These findings suggest a critical role for calcium-permeable AMPA receptors in the altered synaptic transmission observed in early AD stages.

Abstract

Alzheimer's disease is a neurodegenerative disease. Recently, alterations in the mesolimbic system have been described, especially in the nucleus accumbens (nAc). We found that intracellular accumulation of Aβ was higher in neurons of the APP/PS1 mice at 10 and 15 days in vitro . At 15 days in vitro (DIV), APP/PS1 accumbal neurons showed alterations in synaptic transmission and neuronal excitability. Specifically, there was an increase in AMPAergic synaptic currents, which was sensitive to the application of NASPM, suggesting a critical role for calcium-permeable AMPA receptors (CP-AMPARs). Our study indicates that this neuronal culture model accurately replicates alterations in the early stages of AD.

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