Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease

Gut microbial metabolites, SCFAs, were related with the occurrence and development of Parkinson's disease (PD). But the effects of different short-chain fatty acids (SCFAs) on PD and involving mechanisms are still undefined. In this study we evaluate the effects of three dominant SCFAs (acetate, propionate and butyrate) on motor damage, dopaminergic neuronal degeneration and underlying neuroinflammation related mechanisms in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. High (2.0 g/kg) or low doses (0.2 g/kg) of sodium acetate (NaA), sodium propionate (NaP) or sodium butyrate (NaB) were gavaged into PD mice for 6 weeks. High doses of NaA reduced the turning time of PD mice. NaB significantly reduced the turning and total time in pole test, and increased the average velocity in open field test when compared with PD mice, indicating the most effective alleviation of PD-induced motor disorder. Low and high doses of NaB significantly increased the content of tyrosine hydroxylase (TH) by 12.3% and 20.2%, while reduced alpha-synuclein activation by 159.4% and 132.7% in the substantia nigra pars compacta (SNpc), compared with PD groups. Butyrate reached into the midbrain SNpc and suppressed microglia over-activation. It inhibited the levels of pro-inflammatory factors (IL6, IL-1 beta and TNF-alpha) (P < 0.01) and iNOS. Besides, butyrate inhibited the activation of NF-kappa B and MAPK signaling pathways in the SNpc region. Consequently, sodium butyrate could inhibit neuroinflammation and alleviate neurological damage of PD.