Brain metabolism in mice after RhoGTPases pharmacological modulation: a MRI and MRS study

Motivation: RhoGTPases are involved in the pathogenesis of neurodegenerative and neurodevelopmental diseases, playing a key role in synaptic plasticity. Goal(s): The aim is to evaluate the involvement of RhoGTPases on ageing processes, assessing effects of RhoGTPases modulation on behavior and brain metabolism (by MRS) on a healthy aging mouse model. Approach: We pharmacologically modulated RhoGTPases pathways by administering fasudil or CNF1 in mice. Animals are subjected to behavioral tests and to MRI/MRS experiments in frontal cortex, hippocampus and cerebellum. Results: Young mice showed apparent greater anxiolytic effect respect to old mice. We observed also age- differences in the metabolism in response to both treatments. Impact: Dysregulation of the RhoGTPase pathway leads to: oxidative stress, inflammation, alterations in energy metabolism and reduced synaptic transmission. RhoGTPase pathway is involved in the pathogenesis of neurodegenerative diseases; RhoGTPases are here proposed as an innovative pharmacological target for their treatment.