Anxiolytic and anti-stress effects of acute administration of acetyl-L-carnitine in zebrafish.

Lais Pancotto,Angelo Piato,Ricieri Mocelin,Matheus Marcon,Ana P Herrmann

doi:10.7717/peerj.5309

Lais Pancotto, Angelo Piato + Show 3 more

Open Access

https://doi.org/10.7717/peerj.5309

Copy DOI

Abstract

Studies have suggested that oxidative stress may contribute to the pathogenesis of mental disorders. In this context, molecules with antioxidant activity may be promising agents in the treatment of these deleterious conditions. Acetyl-L-carnitine (ALC) is a multi-target molecule that modulates the uptake of acetyl-CoA into the mitochondria during fatty acid oxidation, acetylcholine production, protein, and membrane phospholipid synthesis, capable of promoting neurogenesis in case of neuronal death. Moreover, neurochemical effects of ALC include modulation of brain energy and synaptic transmission of multiple neurotransmitters, including expression of type 2 metabotropic glutamate (mGlu2) receptors. The aim of this study was to investigate the effects of ALC in zebrafish by examining behavioral and biochemical parameters relevant to anxiety and mood disorders in zebrafish. ALC presented anxiolytic effects in both novel tank and light/dark tests and prevented the anxiety-like behavior induced by an acute stressor (net chasing). Furthermore, ALC was able to prevent the lipid peroxidation induced by acute stress in the zebrafish brain. The data presented here warrant further investigation of ALC as a potential agent in the treatment of neuropsychiatric disorders. Its good tolerability also subsidizes the additional studies necessary to assess its therapeutic potential in clinical settings.

Highlights

Acetyl-L-carnitine (ALC) facilitates the movement of acetyl-CoA into the mitochondria during the oxidation of fatty acids in mammals (Chapela et al, 2009)
A growing body of evidence suggests that psychiatric disorders such as anxiety and depression are associated with oxidative damage (Ortiz et al, 2017; Niedzielska et al, 2016; Schiavone, Colaianna & Curtis, 2015; Cobb & Cole, 2015; Ng et al, 2008), since a decrease in antioxidant capacity can impair the organism’s protection against reactive oxygen species and cause damage to fatty acids, proteins, and DNA (Maes et al, 2011)
N-acetylcysteine, resveratrol and curcumin) in the treatment of psychiatric disorders, and it has been reported that these compounds are able to protect against oxidative stress-induced neuronal damage, preventing lipid peroxidation and behavioral changes (Mecocci & Polidori, 2012; Berk et al, 2014; Wang et al, 2014; Mocelin et al, 2015; Patel, 2016; Santos et al, 2017)

Summary

Introduction

Acetyl-L-carnitine (ALC) facilitates the movement of acetyl-CoA into the mitochondria during the oxidation of fatty acids in mammals (Chapela et al, 2009). This molecule is widely consumed as a dietary supplement for physical exercise (Ribas, Vargas & Wajner, 2014; Nicassio et al, 2017). Preclinical and clinical research has evaluated antioxidant compounds (i.g. N-acetylcysteine, resveratrol and curcumin) in the treatment of psychiatric disorders, and it has been reported that these compounds are able to protect against oxidative stress-induced neuronal damage, preventing lipid peroxidation and behavioral changes (Mecocci & Polidori, 2012; Berk et al, 2014; Wang et al, 2014; Mocelin et al, 2015; Patel, 2016; Santos et al, 2017)

Objectives

Methods

Results

Discussion

Conclusion