Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling

Acta Pharmacol Sin. 2010 Jul;31(7):765-74. doi: 10.1038/aps.2010.69. Epub 2010 Jun 28.

Abstract

Aim: To investigate the protective effects of octacosanol in 6-hydroxydopamine-induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins.

Methods: Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD.

Results: Oral administration of octacosanol (35-70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR-sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway.

Conclusion: The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / pharmacology*
  • Antiparkinson Agents / toxicity
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / pharmacology*
  • Fatty Alcohols / toxicity
  • Male
  • Nerve Growth Factor / drug effects
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / drug effects
  • Nerve Growth Factors / metabolism
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Protein Precursors / drug effects
  • Protein Precursors / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkA / metabolism
  • Receptors, Nerve Growth Factor / metabolism

Substances

  • Antiparkinson Agents
  • Fatty Alcohols
  • Nerve Growth Factors
  • Protein Precursors
  • Receptors, Nerve Growth Factor
  • pro-nerve growth factor, rat
  • Ngfr protein, rat
  • 1-octacosanol
  • Oxidopamine
  • Nerve Growth Factor
  • Receptor, trkA
  • Proto-Oncogene Proteins c-akt