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

J Alzheimers Dis. 2025 Nov;108(2):531-538. doi: 10.1177/13872877251378468. Epub 2025 Sep 24.

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.

Keywords: Alzheimer's disease; amyloid-β; cell physiology; electrophysiology; neurobiology.

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Neurons* / physiology
  • Nucleus Accumbens* / cytology
  • Patch-Clamp Techniques
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Receptors, AMPA* / metabolism
  • Synaptic Transmission* / drug effects
  • Synaptic Transmission* / genetics
  • Synaptic Transmission* / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* / pharmacology

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Receptors, AMPA
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid