Dataset Information

Inflammasome-mediated neurodegeneration following heart disease.

ABSTRACT:

Background

Myocardial infarction (MI) has been suggested as a critical predisposing factor for Alzheimer's disease (AD); however, the underlying mechanisms remain unknown. PYD domains-containing protein 3 (NLRP3) is a key factor to mediate inflammasome formation. Previous studies have shown that NLRP3 activation in brain microglia is required for AD; however, its possible role in MI-induced future development of neurodegeneration is not yet understood. These questions were addressed in the current study.

Methods

We generated microglia-specific NLRP3 mutation mice in the AD-prone APP/PS1 background (APP/PS1/NLRP3^MKO), and studied the neurodegeneration in these mice after MI compared to the control wild-type C57/BL6J or APP/PS1 mice. NLRP3, IL-1β and caspase-1 levels were determined by Enzyme-linked immunoassay (ELISA). The heart function was determined by the slope of end systolic pressure-volume relationship, left ventricular end diastolic pressure, the positive maximal pressure derivative as well as the degree of fibrosis by Masson's trichrome staining. Mouse behavior measurement includes Morris water-maze test and motor assessment.

Results

We found that compared with the control wild-type C57/BL6J or APP/PS1 mice, the effects of MI on the subsequent development of defected spatial reference memory and motor activity were all attenuated in APP/PS1/NLRP3^MKO mice, likely resulting from the reduced formation of amyloid-beta peptide aggregates (Aβ) plaques.

Conclusions

NLRP3 may play a non-redundant role in the MI-induced future development of AD.

SUBMITTER: Cheng K

PROVIDER: S-EPMC8576725 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Inflammasome-mediated neurodegeneration following heart disease.

Cheng Kuan K Wang Jingjing J Chen Qingxing Q Zhao Gang G Pang Yang Y Xu Ye Y Ge Junbo J Zhu Wenqing W

Annals of translational medicine 20211001 20

<h4>Background</h4>Myocardial infarction (MI) has been suggested as a critical predisposing factor for Alzheimer's disease (AD); however, the underlying mechanisms remain unknown. PYD domains-containing protein 3 (NLRP3) is a key factor to mediate inflammasome formation. Previous studies have shown that NLRP3 activation in brain microglia is required for AD; however, its possible role in MI-induced future development of neurodegeneration is not yet understood. These questions were addressed in t ...[more]

PMID: 34790766

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Dataset Information

Inflammasome-mediated neurodegeneration following heart disease.

Background

Methods

Results

Conclusions

Publications

Inflammasome-mediated neurodegeneration following heart disease.

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