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Role of the blood-cerebrospinal fluid barrier to neuroinflammation and Alzheimer's disease

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ZAMANI Alemeh HAŠANOVÁ Klaudia YAVIN Nir BRÁZDA Václav JOUKAL Marek

Rok publikování 2022
Druh Konferenční abstrakty
Citace
Popis Alzheimer’s disease (AD) is a progressive neurodegenerative disorder where dementia gradually worsens over a number of years and becomes completely debilitating at later stages. Pathogenesis consists of amyloid-ß peptide (Aß) accumulation and tau protein clusters, leading to neuronal death. Choroid plexus (CP), forming the blood-cerebrospinal fluid barrier, plays a vital role in the clearance of the Aß from the brain. During AD, insufficient clearance of Aß and enhanced inflammatory changes in the CP and cerebrospinal fluid are observed. Despite its clinical importance, our knowledge of the role of the CP in the onset and progression of AD remains rather limited. This study deals with the role of the CP during AD and its potential relationship with neuroinflammation. Using immunocytochemistry, we investigated whether rat choroidal epithelial Z310 cell could uptake the Aß and we observed Z310 cells responses to Aß aggregation inside the cells. Aß aggregation occurred in Z310 cells in a concentration- and time-dependent manner. According to this result, an in vitro model of AD was developed in which the expression of inflammatory mediators, and junctional proteins were examined. Initially, IL-1ß expression increased, while tight junctions were downregulated. Interestingly, zonula occludens-1 returned to its normal level, and the occludin continued to decrease. IL-10 level after 5 days was upregulated. Our data show that Aß aggregation causes an inflammatory response in the CP, which could potentially alter the structure of tight-junction proteins, which are essential for the functionality of the blood-cerebrospinal fluid barrier. In addition, the results support the protective nature of the CP during pathological conditions.

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