ИСТИНА

Aims Amyloid-beta peptide (Abeta) is considered to be as a key protein in the pathogenesis of Alzheimer’s disease because of its neurotoxicity, resulting in impaired synaptic function and memory. On the other hand, it was demonstrated that low (picomolar) concentrations of Abeta enhanced synaptic plasticity and memory. Abeta may act through different targets including acetylcholine and glutamate NMDA receptors. We demonstrated for the first time that strychnine-sensitive glycine receptors can also be the target of Abeta. Method We investigated the effects of Abeta (1-42 and 25-35, 1 pM-100 nM) on the function of different receptors (NMDA, GABA and glycine) in isolated hippocampal pyramidal neurons using whole-cell patch-clamp technique. Results We have found that only glycine-mediated membrane currents were definitely modulated by short (600 ms) glycine co-application with Abeta. Modulation included reversible dose-dependent enhancement of desensitization of glycine current and suppression of its peak amplitude. When Abeta (100 pM) was added to the bath solution, it caused, in addition to acceleration of desensitization, a more pronounced reduction of peak current amplitude. This effect developed slowly and was more prominent at saturating agonist concentrations. Conclusion These results suggest that Abeta interacts with glycine receptors through different mechanisms: by enhancing receptor desensitization and by slowly developing suppression of the current amplitude. The observed changes in the activity of glycine receptors can lead to suppression of the tonic inhibition of hippocampal neurons mediated by extrasynaptic glycine receptors. The disinhibition can benefit different forms of synaptic plasticity, underlying learning and memory. . Supported by the RScF (Grant 16-15-00235).