Exploring the neuroprotective effect of physical activity on the nervous system of mice using different omics

• Grant number: 25/04399-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Andre Schwambach Vieira
• Grantee: Isabela Ribeiro Possebom
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Currently, the literature has widely demonstrated that physical activity promotes health benefits. In the central nervous system (CNS), physical activity promotes neuroplasticity, improves cognition, reduces symptoms of anxiety and depression, and prevents neurodegenerative diseases. However, the mechanisms behind the neuroprotective effects of physical activity have not yet been fully elucidated. In this context, recent studies have shown an increase in the concentration of the endocannabinoid (ECB) anandamide (AEA) and soluble Klotho protein after physical activity in the serum of humans and rodents. ECBs like AEA are important modulators in the CNS, playing a key role in maintaining synapses and controlling neurotransmitter release. Additionally, they can exert a protective effect on various types of neural cells and in neurodegenerative and neurological diseases. Similarly, the Klotho protein generates neuroprotective effects through its antioxidant activity and its role in modulating cellular metabolism. Furthermore, increased Klotho expression is also associated with the prevention of neurodegenerative diseases and cognitive improvements. Therefore, both the Klotho protein and the ECB system may be involved in the beneficial effects generated by physical activity. However, more data is still needed in the literature to analyze this hypothesis more comprehensively. It is known that the expression and function of the Klotho protein, as well as ECBs, are sex-dependent. Moreover, the expression of both factors has already been demonstrated in the choroid plexus and cerebrospinal fluid. Since Klotho does not cross the blood-brain barrier, its extensive production in the plexus may be significant for its function in the CNS. Therefore, the present study aims to quantify the concentration of AEA and Klotho in the serum and cerebrospinal fluid of male and female mice subjected to spontaneous physical activity. Additionally, the effects of 21 days of physical activity will be characterized in different brain structures: such as the medial prefrontal cortex (related to executive control, emotional responses, and motivation), the CA1 region of the hippocampus (related to memory and neurogenesis), and the choroid plexus of male and female mice using transcriptomics and metabolomics techniques.