Minocycline alleviates LPS-induced cognitive dysfunction in mice by inhibiting the NLRP3/caspase-1 pathway.
Aging (Albany NY)
; 16(3): 2989-3006, 2024 02 06.
Article
in En
| MEDLINE
| ID: mdl-38329438
ABSTRACT
BACKGROUND:
Growing experimental evidence indicates that cognitive impairment is linked to neuroinflammation. Minocycline (MINO), an antibiotic known for its anti-inflammatory, has shown promise in alleviating cognitive impairment. Nonetheless, the exact mechanism through which MINO improves cognitive impairment is not yet understood.METHODS:
A neuroinflammatory model was establish by utilizing lipopolysaccharide. The assessment of mice's cognitive and learning abilities was conducted through the MWM and Y-maze tests. The evaluation of hippocampal neuronal injury and microglial activation were achieved by performing HE staining and IHC, respectively. To evaluate BV2 cell viability and apoptosis, the CCK-8 and Hoechst 33342/PI staining assays were employed. In order to assess the protein and RNA expression levels of NLRP3, caspase-1, IL-1ß, IL-18, Iba-1, and Bcl2/Bax, WB and RT-qPCR were utilized. Additionally, the inhibitory effect of MINO on apoptosis by targeting the NLRP3/caspase-1 pathway was investigated using Nigericin.RESULTS:
MINO was effective in reducing the time it took for mice to escape from the test, increasing the number of platforms they crossed, and mitigating damage to the hippocampus while also suppressing microglial activation and the expression of Iba-1 in a neuroinflammatory model caused by LPS. Furthermore, MINO improved the viability of BV2 cell and reduced apoptosis. It also had the effect of reducing the expression levels of NLRP3/Caspase-1, IL-1ß, IL-18, and BAX, while upregulating the expression of Bcl2. Additionally, MINO was found to downregulate the NLRP3 expression, which is specifically activated by nigericin.CONCLUSION:
The protective effect of MINO relies on the crucial involvement of the NLRP3/caspase-1 pathway.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cognitive Dysfunction
/
NLR Family, Pyrin Domain-Containing 3 Protein
Limits:
Animals
Language:
En
Journal:
Aging (Albany NY)
Journal subject:
GERIATRIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: