Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade

Brain Res. 2015 Sep 16;1620:42-56. doi: 10.1016/j.brainres.2015.04.043. Epub 2015 Apr 29.

Abstract

Neuronal apoptosis occurs as a sequel of oxidative stress associated with various neuropathies. In this study, we have investigated the protective effect of farnesol, a sequisterpene on lipopolysaccharide (LPS) induced neurodegeneration through modulation of intrinsic apoptotic cascade in the cortex and hippocampus of Swiss albino mice. Intraperitoneal (i.p.) injection of LPS (250 μg/kg b.wt. for 7 days) resulted in elevated levels of lipid peroxidation, protein carbonyls and 8-Hydroxydeoxyguanosine (8OHdG), with subsequent depletion in the antioxidant status and severe histological aberrations. These anomalies were accompanied by increased expressions of pro-apoptotic Bax, caspase-3 and p53 with decrease in anti-apoptotic Bcl-2. Farnesol treatment (100mg/kg b.wt.) ameliorated LPS-induced oxidative stress by enhancing the antioxidant defense system as evident from the increased levels of SOD, CAT, GSH and GST and exhibited protected cellular morphology manifested from histopathological and nissl staining analyses. Farnesol treatment also reduced the expulsion of cytochrome c from mitochondria and downregulated caspase 3 activation as revealed by immunoblot analysis. Furthermore, farnesol treatment reduced the expression of Bax and antagonized LPS-induced decrease in anti-apoptotic Bcl-2. Results of this study show that farnesol exerts neuroprotective effect by regulating intrinsic apoptotic cascade through its antioxidant effect during LPS-induced neurodegeneration.

Keywords: Apoptosis; Farnesol; Lipopolysaccharide; Neurodegeneration; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / pathology
  • CA1 Region, Hippocampal / physiopathology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Escherichia coli
  • Farnesol / pharmacology*
  • Lipopolysaccharides
  • Male
  • Mice
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Random Allocation

Substances

  • Antioxidants
  • Lipopolysaccharides
  • Neuroprotective Agents
  • Farnesol