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Abstract #4126

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

Valentina Zecca1,2, Teresa Dipol3,4, Gianmauro Palombelli1, Taljinder Singh1,2, Andrea Fortuna3, Ornella Morsilli3, Laura Ricceri5, Stefano Loizzo3, and Rossella Canese1
1MRI Unit, Core Facilities, Istituto Superiore di Sanita', Rome, Italy, 2Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy, 3Department of Cardiovascular, Endocrine-Metabolic and Ageing-Associated Diseases, Istituto Superiore di Sanita', Rome, Italy, 4Department of Physiology and Pharmacology “V. Erspamer, Sapienza University of Rome, Rome, Italy, 5Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanita', Rome, Italy

Synopsis

Keywords: Preclinical Image Analysis, Spectroscopy, animals, aging, spectroscopy, treatment, Rho GTPases

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.

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Keywords