Impact of DHA intake in a mouse model of synucleinopathy

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 α-synuclein (αSyn) 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 αSyn under the Thy-1 promoter (Thy1-αSyn) 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-αSyn 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-αSyn 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-αSyn mice (+51% survival rate at 12months 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 αSyn monomers and oligomers were detected in the cortex of Thy1-αSyn mice, the effects of the diets were limited to a small increase of 42kDa 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 α-synucleinopathy without a major impact on the dopamine system and motor impairments, nor αSyn levels.

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease

“…High levels of polyunsaturated fatty acids (PUFA), such as the omega-3 fatty acid docosahexaenoic (DHA), have been shown to induce anti-inflammatory effects and reduce mitochondrial dysfunction-mediated motor symptoms together with decreasing alpha-synuclein accumulation and inflammation in PD animal models [ 102 , 104 , 105 , 106 , 107 ]. DHA inhibits, whereas saturated fatty acids can activate, certain TLR-mediated pro-inflammatory signaling pathways.…”

The Role of Lipids in Parkinson’s Disease

“…Interestingly, a diet poor in omega-3 PUFA (with or without DHA supplementation) did not affect α-synuclein expression [114]. Accordingly, a DHA-rich diet had no effect on the DA system, motor impairments or α-synuclein levels in α-synuclein-overexpressing mice but increased the longevity of the mice [115]. This latter phenomenon might be related to the role of monomeric α-synuclein in sequestering early DHA peroxidation products and thus reducing oxidative stress [116].…”

Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety

“…Since the discovery of omega-3 (ω3) PUFAs in 1929 by George Burr and Mildred Burr ( Burr and Burr, 1929 ; Spector and Kim, 2015 ), research on ω3 PUFAs became an appealing topic ranging from their role in cardiovascular risk to more recently neuropsychiatric pathologies such as depression and anxiety, cognitive decline or neurodegenerative diseases ( Bazinet and Layé, 2014 ; Joffre et al, 2014 ; Coulombe et al, 2017 ). The relevance of lipids in brain function is illustrated by the fact that the CNS has the highest concentration of lipids in the organism after the adipose tissue (50–60% of the dry weight of the brain; Sastry, 1985 ).…”