Abstract
ABSTRACTIntroduction: 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.
Highlights
Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer’s disease (AD), both highly prevalent pathologies among the elderly
An increment in the mRNA expression levels of IL-1β, IL-6, IL-17 and TNF-α was detected in serotype b-treated cells compared with the non-induced controls (Table 2) and to those treated with serotype a and c, respectively
Higher expression levels of TLR2 mRNA was detected on microglia treated with LPS from serotype a or b compared with LPS from serotype non-induced controls (Table 2)
Summary
Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer’s disease (AD), both highly prevalent pathologies among the elderly. 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. 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. Despite the known implication of Aa in the aggressive forms of PDis and the link clinical link between PDis and AD, which is already known to involve the participation of P. gingivalis, the possible implications of Aa in the etiology and/or progression of AD have not been reported to date
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