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Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease

M. Bousquet^*,, M. Saint-Pierre, C. Julien^*,, N. Salem, Jr.^||, F. Cicchetti^,,1,2 and F. Calon^*,,1,2

^* Centre de Recherche en Endocrinologie Moléculaire et Oncologique, and

Centre de Recherche en Neurosciences, Centre Hospitalier de l’Université Laval (CHUL), Centre Hospitalier Universitaire de Québec (CHUQ), Québec, Canada;

Faculté de pharmacie, and

Département de Médecine, Université Laval, Québec, Canada; and

^|| Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA

²Correspondence: F. Calon, Centre de Recherche du CHUL (CHUQ), Endocrinologie moléculaire et Oncologique, T2–05, 2705, Blvd. Laurier, Québec, QC, G1V 4G2, Canada. E-mail: frederic.calon{at}crchul.ulaval.ca; F. Cicchetti, Centre de Recherche du CHUL (CHUQ), Neurosciences, RC-9800, 2705, Blvd. Laurier, Québec, QC, G1V 4G2, Canada. E-mail: francesca.cicchetti{at}crchul.ulaval.ca

In this study, we examined whether omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may exert neuroprotective action in Parkinson’s disease, as previously shown in Alzheimer’s disease. We exposed mice to either a control or a high n-3 PUFA diet from 2 to 12 months of age and then treated them with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 140 mg/kg in 5 days). High n-3 PUFA dietary consumption completely prevented the MPTP-induced decrease of tyrosine hydroxylase (TH)-labeled nigral cells (P<0.01 vs. MPTP mice on control diet), Nurr1 mRNA (P<0.01 vs. MPTP mice on control diet), and dopamine transporter mRNA levels (P<0.05 vs. MPTP mice on control diet) in the substantia nigra. Although n-3 PUFA dietary treatment had no effect on striatal dopaminergic terminals, the high n-3 PUFA diet protected against the MPTP-induced decrease in dopamine (P<0.05 vs. MPTP mice on control diet) and its metabolite dihydroxyphenylacetic acid (P<0.05 vs. MPTP mice on control diet) in the striatum. Taken together, these data suggest that a high n-3 PUFA dietary intake exerts neuroprotective actions in an animal model of Parkinsonism.—Bousquet, M., Saint-Pierre, M., Julien, C., Salem, N., Jr., Cicchetti, F., Calon, F. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease.

Key Words: MPTP • neuroprotection • DHA • dopamine