Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1401-8. doi: 10.1016/j.pnpbp.2009.07.018. Epub 2009 Jul 24.

Abstract

While we recently reported the beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in a mouse model of Parkinson's disease (PD), the mechanisms of action remain largely unknown. Here, we specifically investigated the contribution of the brain-derived neurotrophic factor (BDNF) to the neuroprotective effect of n-3 PUFA observed in a mouse model of PD generated by a subacute exposure to MPTP using a total of 7 doses of 20mg/kg over 5 days. The ten-month high n-3 PUFA treatment which preceded the MPTP exposure induced an increase of BDNF mRNA expression in the striatum, but not in the motor cortex of animals fed the high n-3 PUFA diet. In contrast, n-3 PUFA treatment increased BDNF protein levels in the motor cortex of MPTP-treated mice, an effect not observed in vehicle-treated mice. The mRNA expression of the high-affinity BDNF receptor tropomyosin-related kinase B (TrkB) was increased in the striatum of MPTP-treated mice fed the high n-3 PUFA diet compared to vehicle and MPTP-treated mice on the control diet and to vehicle mice on the high n-3 PUFA diet. These data suggest that the modulation of BDNF expression contributes, in part, to n-3 PUFA-induced neuroprotection in an animal model of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Fatty Acids, Omega-3 / administration & dosage*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / administration & dosage*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / diet therapy*
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / pathology
  • RNA, Messenger / metabolism
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Dopamine Plasma Membrane Transport Proteins
  • Fatty Acids, Omega-3
  • Neuroprotective Agents
  • RNA, Messenger
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Receptor, trkB
  • Dopamine