Effects of P2Y2 Receptor Antagonism on Hippocampal Calcium Dynamics in a mouse model of Alzheimer's disease

• Grant number: 26/05970-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 01, 2026
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Guilherme Oliveira Carlos
• Supervisor: Alexandre Surget
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université François-Rabelais, France
• Associated to the scholarship: 25/14554-5 - Role of purinergic receptors P2Y2 and P2Y14 in 5xFAD neural progenitor cells at the neonatal stage, BP.IC

Abstract

Alzheimer's disease (AD) involves early disruption of hippocampal circuit function, contributing to episodic and spatial memory deficits. Miniscope calcium imaging enables population recordings in freely moving animals and quantification of population coordination and representational stability. The signaling mechanisms that modulate hippocampal dynamics and may initiate early hippocampus-dependent dysfunctions in AD remain unclear. Neuroinflammation appears to be instrumental to early hippocampal circuit alterations observed in amyloidogenic models, yet how specific pathways shape population dynamics under inflammatory challenge is poorly characterized. Purinergic signaling may link extracellular nucleotide dynamics, neuroinflammation, and neural and glial function. The P2Y2 receptor couples to Gq/PLC/IP3 signaling and mobilizes intracellular Ca2+, positioning it to influence circuit excitability and neuroimmune responses. Genetic evidence suggests that P2Y2 receptor loss exacerbates early pathological features in amyloidogenic contexts. Using miniscope imaging, this project will test whether pharmacological modulation of the P2Y2 receptor alters hippocampal [Ca2+]i dynamics in freely moving APPswe/PS1 mice during tasks relevant to AD-associated symptoms and in relation to neuropathological alterations, comparing vehicle and the selective P2Y2 receptor antagonist AR-C118925XX. (AU)