Abstract
The aggregation of alpha-synuclein protein (αSyn) is a hallmark of Parkinson’s disease (PD). Considerable evidence suggests that PD involves an early aggregation of αSyn in the enteric nervous system (ENS), spreading to the brain. While it has previously been reported that omega-3 polyunsaturated fatty acids (ω-3 PUFA) acts as neuroprotective agents in the brain in murine models of PD, their effect in the ENS remains undefined. Here, we studied the effect of dietary supplementation with docosahexaenoic acid (DHA, an ω-3 PUFA), on the ENS, with a particular focus on enteric dopaminergic (DAergic) neurons. Thy1-αSyn mice, which overexpress human αSyn, were fed ad libitum with a control diet, a low ω-3 PUFA diet or a diet supplemented with microencapsulated DHA and then compared with wild-type littermates. Our data indicate that Thy1-αSyn mice showed a lower density of enteric dopaminergic neurons compared with non-transgenic animals. This decrease was prevented by dietary DHA. Although we found that DHA reduced microgliosis in the striatum, we did not observe any evidence of peripheral inflammation. However, we showed that dietary intake of DHA promoted a build-up of ω-3 PUFA-derived endocannabinoid (eCB)-like mediators in plasma and an increase in glucagon-like peptide-1 (GLP-1) and the redox regulator, Nrf2 in the ENS. Taken together, our results suggest that DHA exerts neuroprotection of enteric DAergic neurons in the Thy1-αSyn mice, possibly through alterations in eCB-like mediators, GLP-1 and Nrf2.
Highlights
Parkinson’s disease (PD) is a common progressive neurological disorder that causes motor and non-motor dysfunctions [1]
Fatty acid composition analysis in plasma revealed the efficacy of the docosahexaenoic acid (DHA) diet to increase circulating levels of DHA, eicosapentaenoic acid (EPA), docosapentaenoic acid (ω-3 DPA) and stearidonic acid (SDA)
The opposite can be observed in animals fed the low ω-3 Polyunsaturated Fatty Acid (PUFA) diet in which DHA, EPA and SDA plasma levels are lower (Table 1)
Summary
Parkinson’s disease (PD) is a common progressive neurological disorder that causes motor and non-motor dysfunctions [1]. It has been shown that pathological damage leading to a moderate or severe loss of neurons in the substantia nigra pars compacta (SNpc) underlies motor symptoms [3,4]. The connection between the ventrolateral SNpc and the dorsal region of the striatum, called the nigrostriatal pathway, is probably the most affected, resulting in 50 to 70% neuronal loss at diagnosis [5]. It is notable that the expression of mutations in this autosomal dominant gene seems to cause early development with rapid progression of the disease and prevalence for psychiatric disorders [14]
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