Subchronic administration of creatine produces antidepressant-like effect by modulating hippocampal signaling pathway mediated by FNDC5/BDNF/Akt in mice

Journal of Psychiatric Research
Mauricio P CunhaAna Lúcia S Rodrigues

Abstract

Creatine has been shown to play a significant role in the pathophysiology and treatment of major depressive disorder (MDD) in preclinical and clinical studies. However, the biological mechanisms underlying its antidepressant effect is still not fully elucidated. This study investigated the effect of creatine (p.o.) administered for 21 days in the behavior of mice submitted to tail suspension test (TST), a predictive test of antidepressant activity. Creatine reduced the immobility time in the TST (1-10 mg/kg), without affecting locomotor activity, a finding consistent with an antidepressant profile. Creatine administration increased the ubiquitous creatine kinase (uCK) and creatine kinase brain isoform (CK-B) mRNA in the hippocampus of mice. Taking into account that PGC-1α induces FNDC5/irisin expression mediating BDNF-dependent neuroplasticity, the effect of creatine administration (1 mg/kg, p. o.) on the hippocampal PGC-1α, FNDC5 and BDNF gene expression was investigated. Creatine treatment increased PGC-1α, FNDC5 and BDNF mRNA in the hippocampus as well as BDNF immunocontent. The involvement of BDNF downstream intracellular signaling pathway mediated by Akt, proapoptotic proteins BAX and BAD and antiapoptotic proteins Bcl2 an...Continue Reading

Citations

Aug 28, 2019·Biomolecules·Brent M KiousPerry F Renshaw
Jan 25, 2020·Journal of Neural Transmission·Aline SiteneskiAna Lúcia S Rodrigues
Apr 8, 2020·Cell & Bioscience·Farzaneh RabieeKamran Ghaedi
Jun 20, 2019·Nutrients·Dylan O'Neill Rothenberg, Lingyun Zhang
Sep 3, 2021·Molecular Psychiatry·Juncai PuPeng Xie

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