by Dr. Micaela Zonta, CNR Neuroscience Institute
When: October 31, 2024, at 3:00 pm
Where: Aula RI (Complesso Vallisneri, Viale Colombo 3, Padova)
Abstract: Alzheimer’s disease (AD) is a chronic, incurable neurodegenerative disorder, characterized by progressive memory loss. Despite the advances in the research on neurodegenerative diseases, the molecular and cellular mechanisms underlying AD pathogenesis and the early events that anticipate the cognitive decline remain poorly understood.
Our research evaluates the involvement of astrocytes in AD pathogenesis, focusing on astrocyte Ca2+ signaling and its dysregulation during AD progression. Indeed, the widely recognized evidence that brain function requires dynamic interactions between neurons and astrocytes implies that both cell types can contribute to brain dysfunction.
We employ two-photon microscopy to perform Ca2+ imaging experiments in brain slices and in vivo preparations of somatosensory cortex (SSCx) astrocytes expressing GCaMP6f, and electrophysiological monitoring to assess the efficiency of long-term memory processes. We describe significant alterations in astrocyte activity in the familial AD model PS2APP, as well as in astrocyte-dependent long-term plasticity and reveal the molecular mechanisms underlying Ca2+ dysregulation. Most importantly, we describe a genetic strategy to rescue astrocyte signals and synaptic plasticity.
Our data identify the dysregulation of astrocyte Ca2+ activity as a functional hallmark of early AD stages, revealing a new target to recover AD symptoms.