Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice

Chem Biol Interact. 2022 Sep 25:365:110059. doi: 10.1016/j.cbi.2022.110059. Epub 2022 Aug 3.

Abstract

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

Keywords: Cholinergic system; Epilepsy; Monoamines; Oxidative stress; Pilocarpine; Trans,trans-farnesol.

MeSH terms

  • Animals
  • Dopamine
  • Epilepsy* / drug therapy
  • Farnesol / adverse effects
  • Hippocampus
  • Mice
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Norepinephrine / pharmacology
  • Pilocarpine / toxicity
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Serotonin

Substances

  • Neuroprotective Agents
  • Pilocarpine
  • Serotonin
  • Farnesol
  • Dopamine
  • Norepinephrine