Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?
Author
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Díaz Zúñiga, J.
Author
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Muñoz, Y.
Author
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Melgar Rodríguez, Samanta
Author
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More, J.
Author
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Bruna, B.
Author
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Lobos, P.
Author
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Monasterio, G.
Author
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Vernal Astudillo, Rolando
Author
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Paula Lima, A.
Admission date
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2019-10-22T03:15:02Z
Available date
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2019-10-22T03:15:02Z
Publication date
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2019
Cita de ítem
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Journal of Oral Microbiology, Volumen 11, Issue 1, 2019,
Identifier
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20002297
Identifier
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10.1080/20002297.2019.1586423
Identifier
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https://repositorio.uchile.cl/handle/2250/172066
Abstract
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Introduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer’s disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD.
Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?