Ricerc@Sapienza

Background Aging is a time-related deterioration of physiological functions, associated with chronic oxidative stress and inflammation. The brain, with proliferation limit of its cells, is particularly affected by it. Brain aging presents cognitive alterations and involves microglia (MG), responsible for the chronic neuroinflammation, that causes morpho-functional alteration of astrocytes (AS). AS lose the ability to maintain the physiological levels of glutamate (Glu). This leads to neuronal death. All these alterations cause memory loss and lack of motor coordination that occur with aging. MG and AS reactivities are linked to gender explaining the neuroprotective effects of sex steroids after brain injury. MG responds to estrogen by reducing its inflammatory response; AS distribution, reactivity, and interaction with other cells of the brain depend on gender. Extracellular vesicles (EVs) represent a mode of information exchange between donor and recipient cells.
Hypothesis The project proposes the exogenous administration of EVs deriving from "young" microglia or astrocytes to old mice to slow down neuroinflammation in aging. Objective To evaluate the effects of the administration of EVs deriving from ¿young¿ or ¿old¿ glial cells to mice of different sexes, to measure their efficacy in the aging processes linked to intercellular cross-talk. Experimental project EVs released from primary mouse MG and AS will be used to be administered to male and female mice. Aging will be evaluated in vivo as motor skills and memory, and ex vivo as level of neuroinflammation, neuronal death and synaptic plasticity. Expected results i) reduction of neuroinflammation slowdowns memory impairment and motor reflexes in old mice treated with EVs derived from ¿young¿ cell cultures; ii) acceleration of aging process in "young" mice treated with EVs derived from "old" cell cultures; iii) anti-aging effects of EVs from ¿young¿ cells in female mice more exhaustive compared to male mice.