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

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

Kaynakça

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