Acute Peripheral Irisin Administration Increases Hippocampal Mass in Young, Healthy Rat Cohort

Abstract

Introduction: Skeletal muscle-brain crosstalk is highlighted as an important contributor to the beneficial relationship between exercise and the brain. Irisin is a key crosstalk myokine due to the ability of irisin to cross the blood-brain barrier and mediate effects of exercise in the brain. Importantly, the influence of irisin in the brain is often demonstrated through chronic administration or supraphysiological dosing of irisin. The aim of the present study is to determine if an acute, non-supraphysiological dose of exogenous irisin is suffcient to induce previously established effects in the hippocampi of young, healthy rats. Methods: Twenty-four 2–3-month-old male and female F344 rats were divided into two groups of 12 (50% male/female) which either received an irisin (100 μg/kg) or vehicle intraperitoneal injection. Forty-eight hours following irisin injections, brains were sectioned and weighed. Levels of total and phosphorylated hippocampal cyclic-AMP Response Element Binding Protein (CREB), a downstream target of irisin signaling, were quantified with Jess Simple Western automated western blot analysis. Values are mean ± standard deviation. Results: Irisin administration resulted in greater hippocampi mass (relative to brain mass, %) compared to vehicle treated animals (3.65±0.24 vs 3.28±0.32%, p<0.01). Further, pCREB/CREB in the hippocampus of irisin animals (0.58±0.13) was 24.6% greater than vehicle (0.47±0.09, p<0.05). Irisin administration did not influence body mass or whole brain mass relative to body mass. Conclusions: The present study demonstrates that a non-supraphysiological dose of irisin is suffcient to increase hippocampal mass and CREB phosphorylation 48 hours post-injection. This work supports irisin as an important, physiologically relevant mediator of the beneficial relationship between exercise, skeletal muscle, and the brain. NIH P20GM113109. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.