LACTIC ACID BACTERIA REDUCED PRO-INFLAMMATORY CYTOKINES EXPRESSION AND OXIDATIVE STRESS ON BV-2 MICROGLIA CELLS STIMULATED WITH AMYLOID BETA OLIGOMERS.

BULACIOS, GABRIELA AGUSTINA; CATALDO, PABLO GABRIEL; ELEAN, MARIANO; ELENA POSSE DE CHAVES; DUPUY, FERNANDO G.; CARLOS MINAHK; E. M. HEBERT; SAAVEDRA LUCILA

Congreso; SAIB 2021; 2021

Neuroinflammation and oxidative stress are recognized hallmarks of neurodegenerative diseases, including Alzheimer?s disease (AD). Activation of microglia has been proposed to be one of the first steps in the onset of AD. Microglia produce and secrete neurotoxic compounds and pro-inflammatory cytokines. Lactic acid bacteria (LAB) are well known microorganisms and are widely studied for their various benefits to human health. Currently, there is an increasing interest in using LAB in alternative therapies because of the potential role that gut microbiota play in the pathogenesis of Alzheimer´s disease. In the present study, we examined the effects of three LAB strains on oxidative stress and inflammation-related gene expression in BV-2 microglial cells stimulated with amyloid beta oligomers (oAβ1-42). BV-2 cells were treated with 5 µM oAβ and the effect of LAB was evaluated under three different conditions: using living bacteria, heat-inactivated bacteria, and bacterial conditioned media (BCM). After 8 hours of treatment, BV2 cells and supernatants were harvested separately. Total RNA was extracted from BV2 cells and the expression of TNF-α, IL-1β, IL-6, iNOS and SOD was examined by RT-qPCR. Treatments with living and dead bacteria did not show any significant changes in mRNA expression of the evaluated genes with respect to control groups. Nevertheless, BCM from Enterococcus mundtii CRL 35, Lactobacillus delbrueckii subsp. lactis CRL 581 and Levilactobacillus brevis CRL 2013 significantly reduced IL-1β and IL-6 expression. Additionally, TNF-α expression was down-regulated on BV-2 cells treated with BCM from CRL 35. No significant differences were found in iNOS and SOD expression. Finally, total antioxidant activity of all supernatants from BV-2 cells treated with BCM was measured using both the ABTS decolorization assay and the CUPRAC assay. We found that the supernatants from microglia cells treated with BCM from CRL 35 were capable of reducing cupric ions and ABTS+ cations, indicating a significant antioxidant activity. Our results show that conditioned media from E. mundtii CRL 35, L. delbrueckii subsp. lactis CRL 581 and L. brevis CRL 2013 have the ability to reduce inflammatory and oxidative stress markers produced by amyloid beta oligomers in vitro. We are currently examining the mechanisms and LAB metabolites implicated in these effects.