Aging and adenosinergic modulation of hippocampal excitability and synaptic plasticity.

• Grant number: 23/02046-0
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2024 - October 31, 2026
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: Roberto De Pasquale
• Grantee: Roberto De Pasquale
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alexander Henning Ulrich ; Guilherme de Araujo Juvenal
• Associated scholarship(s): 24/14705-0 - Adenosinergic modulation in hippocampal synaptic excitability and plasticity during aging, BP.TT

Abstract

The aging nervous system undergoes a series of modifications that predispose it to pathological changes that include memory deficits. The formation of explicit memory traces is based on the neural functions of the hippocampus. Through synaptic plasticity, this region reorganizes its circuitry, allowing the consolidation and recovery of acquired information. Hyperexcitation of the hippocampal circuit has been suggested as a possible cause responsible for the decline in memory and plasticity of the hippocampus during aging. Adenosine neuromodulation may play an important role in this context, considering that, in the hippocampus of the elderly brain, the inhibitory activity of A1 receptors is reduced while the excitatory activity of A2A receptors is increased. Using a mouse model of accelerated aging (SAMP-8), this project proposes the performance of behavioral tests, molecular biology techniques and in vitro electrophysiology experiments, with the objective of studying the effects of advanced age on memory, excitability neuronal and synaptic plasticity of the hippocampus, focusing on the neuromodulatory role of adenosine. According to our hypothesis, in the young hippocampus, A1 receptors would have a protective and homeostatic role on excitability, while A2A receptors would be selectively recruited in the induction of plasticity. In the elderly hippocampus, however, excessive stimulation of A2A receptors would lead to pathological hyperexcitability of the circuitry, which would generate a dysfunction in the mechanisms of synaptic plasticity and, consequently, an impairment in the formation of memory traces. (AU)