INVESTIGADORES
SAAVEDRA Maria Lucila
congresos y reuniones científicas
Título:
Selection of lactic acid bacteria strains able to modulate the host central nervous system
Autor/es:
BULACIOS, GABRIELA AGUSTINA; SALAZAR PAULA BELEN; POSSE DE CHAVES, ELENA; HEBERT EM; MINAHK, CARLOS; SAAVEDRA, LUCILA
Lugar:
Salta
Reunión:
Congreso; LV Annual SAIB Meeting and XIV PABMB Congress; 2019
Resumen:
Current evidence indicates that modulation of the central nervous system (CNS) by the microbiome occurs primarily through neuroimmune and neuroendocrine mechanisms, often involving the vagus nerve. In fact, the gut-brain axis provides the intestinal bacteria and its metabolites a way to get access to the brain, thus regulating the expression of key effectors. Although lactic acid bacteria (LAB) represent only a small percentage of the total gut-dwelling microorganisms, they are undoubtedly important players. Pro-inflammatory cytokines are naturally upregulated in the elderly and gut microbiota undergoes changes during aging. Therefore, it has been proposed that administration of probiotics may decrease the synthesis of these pro-inflammatory cytokines, hence reducing inflammation and oxidative stress, ameliorating the effects of senescence and the progression of neurodegenerative diseases often associated to aging. These facts strongly suggest that LAB may be an invaluable tool in the treatment of aging-related pathologies such as Alzheimer?s disease (AD), where microglia and non-parenchymal macrophages drive the neurodegeneration via neuroinflammation. The aim of the present work was to assess the capacity of different LAB strains metabolites to regulate the secretion of cytokines, inhibit acetylcholinesterase (AChE) and protect cells from the cytotoxic effects of the Aβ oligomers, key features of AD. For that purpose, murine RAW 264.7 macrophages were treated with conditioned media from seven selected LAB strains prior to the LPS stimulation. The mRNA expression levels of the tumor necrosis factor alpha (TNF)-α, interferon-gamma (IFN-γ) and interleukin IL10 were examined by RT-PCR. The results showed that conditioned media from Lactobacillus delbrueckii subsp. lactis CRL 581 and Lactobacillus reuteri CRL 1098 significantly inhibited TNF-α mRNA expression. In addition, CRL 1098 strain increased IL-10 mRNA expression level in LPS-stimulated RAW 264.7 cells. Then, all conditioned media were evaluated in their ability to inhibit AChE from human erythrocytes (AChE-E) by Ellman´s method. AChE-E constitutes a model of the isoform present in the CNS. As controls, polyphenols previously characterized as efficient inhibitors of AChE as well as strong anti-inflammatory agents were used. Conditioned media from L. delbrueckii subsp. lactis CRL 581 showed a 40% inhibition of enzymatic activity. Finally, APP-expressing neuroblastoma cells were preincubated with conditioned media and the expression of the APP transgene was induced by butyric acid. Viability of cells were evaluated using alamar blue assay. Results evidenced that conditioned media from L. rhamnosus A29 and Enterococcus mundtii CRL 35 protected against Aβ induced neuron cytotoxicity. These preliminary data support our ongoing investigations regarding the molecular mechanism of LAB interactions in the gut brain axis.