Protocol for Exploring the Role of Irisin in the Enhancement of Spatial Learning Mediated by Aerobic Physical Exercise in Adult Mice

Abstract

Introduction: Age-related cognitive decline decreases with aerobic physical exercise in many animal models and humans. Irisin, a myokine and its’ precursor FNDC5, has increased hippocampal development to improve learning and memory. This study aims to determine the association between irisin, physical activity and enhancement of spatial learning in adult mice.

Methods: Three experimental studies will be conducted to explore the role of FNDC5/irisin in spatial learning. Study 1 will test the spatial learning ability in C57BL/6 mice using Morris Water Maze (MWM) task in WT, FNDC5+/- and FNDC5-/- mice strains. Study 2 will test the changes in the MWM task due to exogenous administration of FNDC5/irisin in the hippocampus, specifically in the dentate gyrus region. Study 3 aims to test the effect of aerobic physical activity on irisin levels in the dentate gyrus region and the changes in the MWM task.

Anticipated Results: Study 1 results are expected to show that WT mice perform better compared to the FNDC5+/- and FNDC5-/- in completing the MWM task. Study 2 is anticipated to show that hippocampal administration of FNDC5/irisin can rescue the spatial learning phenotype. Study 3 is expected to show that PE improves spatial learning in all mice strains by regulating FNDC5/irisin levels.

Discussion: FNDC5/irisin play a role in enhancing neurogenesis and synaptic plasticity by regulating downstream signalling pathways that are involved in cognitive functions. Aerobic PE enhances this mechanism, resulting in improved spatial learning.

Conclusion: Aerobic PE is expected to significantly regulates hippocampal FNDC5/irisin, which is associated with enhancing spatial learning and cognitive functions.