Association of folate production and immune modulation by seleceted bacteria in Parkinson's disease models

Abstract

Parkinson's disease (PD) is a neurodegenerative process that affect motor functions and involves an inflammatory response and B group vitamins' deficiency. Folate depletion with hyperhomocysteinemia are related with immune activation ; however, the association between folate (vitamin B9) and the immune system in PD requires further research. Aim: To evaluate the effect of folate-producing and immunomodulatory lactic acid bacteria (LAB) in PD models. Methods. Streptococcus thermophilus (St.) CRL808 (folate producer strain), and St. CRL807 (immunomodulatory strain) were evaluated individually using in vitro and in vivo PD models. N2a neuronal cells were differentiated to dopaminergic neurons with di-butyryl cyclic AMP and then exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) in presence of intracellular extracts from LAB or the commercial vitamin B9. Cell viability, IL-6 production and reactive oxygen species (ROS) were determined. In vivo, LAB were administered to mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Motor capacity, tyrosine hydroxylase (TH) in brain, and cytokines in serum were evaluated. Results: Neurotoxic effect of MPP+ decreased in cells cultured with both LAB intracellular extracts. This result was related with significant (p<0.05) decrease of ROS formation and IL-6 release by the neurons Mice given LAB improved motor skills altered by MPTP and significantly (p<0.05) increased the number of TH+ neurons in the brain . The LAB effect was associated to decreased pro-inflammatory cytokines such asIL-6 and TNF-alpha and increased levels of IL-10 in the serum of the mice. Conclusions. LAB selected as folate producers and as immunomodulators have the potential to be used as adjuvants in PD, improving both vitamin deficiency and the inflammatory state associated with this pathology, which translates into less loss of dopaminergic neurons and better motor skills.