Abstract
Background: Accumulation of the α-synuclein (α-syn) protein and depletion of dopaminergic neurons in the substantia nigra are hallmarks of Parkinson’s disease (PD). Currently, α-syn is under scrutiny as a potential pathogenic factor that may contribute to dopaminergic neuronal death in PD. However, there is a significant gap in our knowledge on what causes α-syn to accumulate and dopaminergic neurons to die. It is now strongly suggested that the nature of our dietary intake influences both epigenetic changes and disease-related genes and may thus potentially increase or reduce our risk of developing PD.Objective: In this study, we determined the extent to which a 3 month diet enriched in the saturated free fatty acid palmitate (PA) influences levels of α-syn and tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis in mice brains.Methods: We fed the m-Thy1-αSyn (m-Thy1) mouse model for PD and its matched control, the B6D2F1/J (B6D2) mouse a PA-enriched diet or a normal diet for 3 months. Levels of α-syn, tyrosine hydroxylase, and the biogenic amines dopamine and dopamine metabolites, serotonin and noradrenaline were determined.Results: We found that the PA-enriched diet induces an increase in α-syn and TH protein and mRNA expression levels in m-Thy1 transgenic mice. We also show that, while it didn’t affect levels of biogenic amine content in the B6D2 mice, the PA-enriched diet significantly reduces dopamine metabolites and increases the level of serotonin in m-Thy1 mice.Conclusion: Altogether, our results demonstrate that a diet rich in the saturated fatty acid palmitate can modulate levels of α-syn, TH, dopamine, and serotonin which all are proteins and neurochemicals that play key roles in increasing or reducing the risk for many neurodegenerative diseases including PD.
Highlights
Hallmarks of Parkinson’s disease (PD) include the loss of dopaminergic neurons containing-tyrosine hydroxylase (TH) in the substantia nigra pars compacta and the abnormal accumulation of α-syn protein in Lewy bodies (Schapira, 1997; Spillantini et al, 1997; Crowther et al, 2000)
Altogether, our results demonstrate that a diet rich in the saturated fatty acid palmitate can modulate levels of α-syn, TH, dopamine, and serotonin which all are proteins and neurochemicals that play key roles in increasing or reducing the risk for many neurodegenerative diseases including PD
We examined the effects of a PA-enriched diet on α-syn protein levels and mRNA expression in the substantia nigraenriched fractions from the B6D2 mice and found that 3 months of feeding with a PA-enriched diet significantly increased (p < 0.05) α-syn protein levels compared to the control diet (Figures 1A,B)
Summary
Hallmarks of PD include the loss of dopaminergic neurons containing-TH in the substantia nigra pars compacta and the abnormal accumulation of α-syn protein in Lewy bodies (Schapira, 1997; Spillantini et al, 1997; Crowther et al, 2000). In vitro studies have shown that while PUFAs increase α-syn oligomerization and insoluble aggregate formation, sFFAs did not (Sharon et al, 2003; Assayag et al, 2007) Many of these epidemiological studies utilized food frequency questionnaires without clarifying the specific role of each sFFAs. In studies carried out in mice, the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to provide neuroprotective effects in animal models of PD (Bousquet et al, 2008, 2011; Seidl et al, 2014; Dyall, 2015).
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