Partial neurorescue effects of DHA following a 6-OHDA lesion of the mouse dopaminergic system

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• 作者：Katherine Coulombe^a ; ^b ; ^{katherine.coulombe.2@ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Martine Saint-Pierre^b ; ^{martine.saint-pierre@crchudequebec.ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Giulia Cisbani^b ; ^c ; ^{Giulia.Cisbani@crchudequebec.ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Isabelle St-Amour^b ; ^c ; ^{Isabelle.St-Amour@crchudequebec.ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Claire Gibrat^b ; ^c ; ^{claire.gibrat@criucpq.ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Ariane Giguè ; re-Rancourt^a ; ^b ; ^{ariane.giguere-rancourt.1@ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Fré ; dé ; ric Calon^a ; ^b ; ¹ ; ^{frederic.calon@crchudequebec.ulaval.ca" class="auth_mail" title="E-mail the corresponding author} ; Francesca Cicchetti^b ; ^c ; ¹ ; ^{francesca.cicchetti@crchudequebec.ulaval.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：6-Hydroxydopamine ; Neurorescue ; Neurorestoration ; Docosahexaenoic acid ; Dopamine ; Parkinson's disease
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：30
• 期：Complete
• 页码：133-142
• 全文大小：1306 K

文摘

Pre-clinical data collected in mouse models of Parkinson's disease (PD) support the neuroprotective potential of omega-3 polyunsaturated fatty acids (n-3 PUFA)-enriched diet on the dopaminergic (DAergic) system. In this study, we investigated the effects of an n-3 PUFA-rich diet using a neurorescue/neurorestorative paradigm. C57BL/6 adult mice were submitted to a striatal stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA) to induce striatal DAergic denervation and subsequent nigral DAergic cell loss. Three weeks post-lesion, mice received either a docosahexaenoic acid (DHA)-enriched or a control diet for a period of 6 weeks. HPLC analyses revealed a 111% post-lesion increase in striatal dopamine levels in the DHA-fed animals compared to controls (ctrl, P<0.05), although no improvement in the motor behavior was observed. DHA treatment led to a 89% rise in tyrosine-hydroxylase (TH)-immunoreactive terminals within the striatum (P<0.05) in lesioned animals. Despite the fact that DHA did not change the number of TH+ neurons in the substantia nigra pars compacta (SNpc), morphological analyses revealed an increased in perimeters (+7%) and areas (+21%) of DAergic cell bodies in treated animals. Collectively, our results suggest that DHA induces a partial neurorescue/neurorestoration of the DAergic system and support further studies to investigate the potential of a diet-based intervention, or at least the combination of such approach, to current treatments in PD.