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ABSTRACT Polyunsaturated fatty acids omega‐3 (n‐3 PUFA), such as docosahexaenoic acid (DHA), have been shown to prevent, and partially reverse, neurotoxin‐induced nigrostriatal denervation in animal models of Parkinson's disease (PD).… Click to show full abstract
ABSTRACT Polyunsaturated fatty acids omega‐3 (n‐3 PUFA), such as docosahexaenoic acid (DHA), have been shown to prevent, and partially reverse, neurotoxin‐induced nigrostriatal denervation in animal models of Parkinson's disease (PD). However, the accumulation of &agr;‐synuclein (&agr;Syn) in cerebral tissues is equally important to the pathophysiology. To determine whether DHA intake improves various aspects related to synucleinopathy, ninety male mice overexpressing human &agr;Syn under the Thy‐1 promoter (Thy1‐&agr;Syn) were fed one of three diets (specially formulated control, low n‐3 PUFA or high DHA) and compared to non‐transgenic C57/BL6 littermate mice exposed to a control diet. Thy1‐&agr;Syn mice displayed impaired motor skills, lower dopaminergic neuronal counts within the substantia nigra (−13%) in parallel to decreased levels of the striatal dopamine transporter (DAT) (−24%), as well as reduced NeuN (−41%) and synaptic proteins PSD‐95 (−51%), synaptophysin (−80%) and vesicular acetylcholine transporter (VChAT) (−40%) in the cerebral cortex compared to C57/BL6 mice. However, no significant difference in dopamine concentrations was observed by HPLC analysis between Thy1‐&agr;Syn and non‐transgenic C57/BL6 littermates under the control diet. The most striking finding was a favorable effect of DHA on the survival/longevity of Thy1‐&agr;Syn mice (+51% survival rate at 12 months of age). However, dietary DHA supplementation did not have a significant effect on other parameters examined in this study, despite increased striatal dopamine concentrations. While human &agr;Syn monomers and oligomers were detected in the cortex of Thy1‐&agr;Syn mice, the effects of the diets were limited to a small increase of 42 kDa oligomers in insoluble protein fractions upon n‐3 PUFA deprivation. Overall, our data indicate that a diet rich in n‐3 PUFA has a beneficial effect on the longevity of a murine model of &agr;‐synucleinopathy without a major impact on the dopamine system and motor impairments, nor &agr;Syn levels. HighlightsDHA improved the survival of Thy1‐&agr;Syn mice.Thy1‐&agr;Syn mice displayed lower nigral dopaminergic neurons and striatal DAT.NeuN, PSD95, VChAT and synaptophysin cortical levels were reduced in Thy1‐&agr;Syn mice.DHA had no major impact on dopaminergic system and motor impairments.DHA had no major impact on brain &agr;Syn levels.