Short-Term Amyloid Beta Application Decreased Glutamate Release, but Increased Glutamate Spillover in Hippocampal Neurons

Year 2023, Volume: 5 Issue: Supplement (1) - Innovations in Medicine and Healthcare in the 100th Year of the Republic, 187 - 91, 19.10.2023

Enis Hidisoglu

https://doi.org/10.37990/medr.1348054

Abstract

Aim: Synaptic dysfunction is a characteristic linked with the early stages of Alzheimer's disease (AD), but the pathological mechanisms remain elusive. It was aimed to investigate how amyloid beta 42 (Abeta42) peptide affects miniature events mediated by glutamate release in hippocampal neurons.
Material and Methods: We performed all experiments in the primary cultured hippocampal neurons in control and Abeta42-treated neurons (24 h). Pharmacologically isolated miniature excitatory postsynaptic currents (mEPSCs) were obtained in whole-cell voltage-clamp configuration at – 70 mV. AMPAergic channel conductance and basic synaptic parameters were evaluated by performing peak-scaled variance analysis and cumulative event analysis and glutamate spillover is determined by application of DNQX.
Results: The oligomeric Abeta42 for 24h decreased the mEPSCs frequency (***p<0.001), while it has no any measurable effect on the amplitude of mEPSCs as well as unitary current and number of receptors. In addition, the incubation of neurons with oligomeric Abeta42 for 24h increased the glutamate spillover measured as baseline shift (***p<0.001).
Conclusion: The oligomeric form of the Abeta42 peptide has a significant effect on the presynaptic site of excitatory synapses in primary cultured hippocampal neurons. It lowers the release probability during short-term incubation, while it increases glutamate spillover.

Keywords

Alzheimer’s disease, amyloid beta peptide, AMPAergic synapses, glutamate spillover

Supporting Institution

University of Turin

Project Number

HIDE_RILO_22_01

Thanks

I express my gratitude to Dr. Andrea Marcantoni and Claudio Franchino for supplying me with primary hippocampal neuron cultures and the essential tools required for performing the experiments.

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