Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model.
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.
Bousquet
M
M
Centre de Recherche du CHUL (CHUQ), Axe Neurosciences, Québec, QC, Canada.
Gibrat
C
C
Saint-Pierre
M
M
Julien
C
C
Calon
F
F
Cicchetti
F
F
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D050483:Dopamine Plasma Membrane Transport Proteins; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D020813:Receptor, trkB; D004298:Dopamine