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Central irisin administration affords antidepressant‐like effect and modulates neuroplasticity‐related genes in the hippocampus and prefrontal cortex of mice

A. Siteneski,M. Cunha,V. Lieberknecht,F. L. Pazini,Karen Gruhn,P. Brocardo,A. Rodrigues

Published 2018 in Progress in Neuro-psychopharmacology and Biological Psychiatry

ABSTRACT

ABSTRACT Evidence has indicated that the practice of physical exercise has antidepressant effects that might be associated with irisin release and BDNF signaling. In this study we investigated the effects of the central administration of irisin or BDNF in predictive tests of antidepressant properties paralleled with the gene expression of peroxisome proliferator‐activated receptor gamma co‐activator 1&agr; (PGC‐1&agr;), fibronectin type III domain‐containing protein 5 (FNDC5) and brain‐derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex of mice. Irisin (0.5–1ng/mouse, i.c.v.) reduced the immobility time in the tail suspension test (TST) and forced swim test (FST), without altering locomotion in the open field test (OFT). Irisin reduced the immobility time in the TST up to 6h after its administration. Irisin administration (6h) increased PGC‐1&agr; mRNA in the hippocampus and prefrontal cortex and reduced (1h) PGC‐1&agr; mRNA in the prefrontal cortex. FNDC5 and BDNF mRNA expression was decreased (1h) in both structures and remained reduced up to 6h in the prefrontal cortex. Moreover, BDNF administered at 0.25&mgr;g/mouse, i.c.v. (1 and 6h before the test) reduced the immobility time in the TST. BDNF administration reduced PGC‐1&agr; mRNA in the hippocampus (6h) and prefrontal cortex (1 and 6h). It also increased FNDC5 mRNA expression in the hippocampus (1 and 6h), but reduced the expression of this gene and also BDNF mRNA in the prefrontal cortex (1 and 6h). None of the treatments altered BDNF protein levels in both structures. In conclusion, irisin presents a behavioral antidepressant profile similar to BDNF, an effect associated with the modulation of gene expression of PGC‐1&agr;, FNDC5 and BDNF, reinforcing the pivotal role of these genes in mood regulation. HIGHLIGHTSCentral administration of irisin and BDNF elicited antidepressant‐like behaviors.Irisin enhanced PGC‐1&agr; mRNA in the hippocampus and prefrontal cortex.FNDC5 and BDNF gene expression was reduced by irisin administration.BDNF administered centrally modulated all these genes in the hippocampus and prefrontal cortex.The levels of BDNF protein were not altered by irisin or BDNF administration.

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