Effect of chronic caffeine consumption on the dynamics of neural networks in the hippocampal formation in a SAMP8 mouse model of accelerated aging.

• Grant number: 25/07125-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Pedro Santos Rosa Muradás
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Aging is characterized by the progressive decline of cellular functions and physiological processes. In the central nervous system, this decline manifests as an increase in neuroinflammation, cellular senescence, accumulation of metabolic waste and neuronal dysfunctions, which compromises synaptic plasticity and, consequently, neuronal communication. Thus, aging favors the development of neurodegenerative diseases and loss of cognitive functions. The hippocampus, for example, is a brain structure that is central to processes such as the consolidation of episodic memory and learning. With aging, there is a decline in hippocampal plasticity and exacerbation of excitotoxic processes, generating deficits in its functions. Another contributing factor is the altered function of neuromodulators, important for regulating hippocampal excitability and synaptic plasticity, such as in the adenosinergic system. The reduction in the inhibitory activity of A1 receptors and an increase in the excitatory activity of A2A receptors, possibly as a compensatory response to aging-induced alterations in excitability, leads to significant changes in hippocampal communication. However, caffeine, by acting as a non-selective antagonist of adenosinergic receptors, can attenuate these changes, restoring the excitatory and inhibitory balance of hippocampal networks and preventing deterioration resulting from aging. Using a mouse model with accelerated aging (SAMP-8) and with the aid of high-density multielectrode arrays (HD-MEA), we will investigate the dynamics of hippocampal networks altered by aging and the effect of caffeine on these dynamics. Thus, this study aims to understand the changes in neuronal dynamics in the hippocampus that give rise to the cognitive changes observed during aging, in addition to evaluating possible stabilizing agents for these networks, such as chronic exposure to caffeine.