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

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.

Integrated application of multi-omics provides insights into cold stress responses in pufferfish Takifugu fasciatus

“…However, this conclusion is derived from studies of human diseases and has not been confirmed in teleosts. A possibility needs to be explored that they may have a similar relationship in teleosts because we found that L-leucine could increase growth performance, improve metabolic activities and enhance non-specific immunities in tilapia [73] and black carp juveniles [74], and acetylcarnitine has antioxidant effects in teleosts [75].…”

Anxiety and Brain Mitochondria: A Bidirectional Crosstalk

“…Although most preclinical work on LAC in humans and rodents has focused on depression [106], existing evidence supports the interest in further exploring its potential anxiolytic effects. LAC supplementation was shown to induce anxiolytic effects in patients with minimal hepatic encephalopathy [107] and in zebrafish [108]. In the latter model, LAC was, as well, able to prevent the lipid peroxidation induced by acute stress [108].…”

“…LAC supplementation was shown to induce anxiolytic effects in patients with minimal hepatic encephalopathy [107] and in zebrafish [108]. In the latter model, LAC was, as well, able to prevent the lipid peroxidation induced by acute stress [108]. It should be noted, though, that other mechanisms of action -such as its reported antioxidant properties [109]-may also be implicated in LAC effects.…”

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

“…Related to its protective role in psychiatric disorders, in zebrafish, ALC prevented acute stress-induced anxiety (Pancotto, Mocelin et al 2018). In mice, ALC treatment (25-100 mg/kg, i.p.)…”