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Severe inflammation in C57/BL6 mice leads to prolonged cognitive impairment by initiating the IL-1β/TRPM2 pathway.
- Source :
-
International Immunopharmacology . Feb2024, Vol. 128, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- • Severe inflammation induces prolonged cognitive impairment among C57/BL6 mice. • Prolonged upsurge in hippocampal IL-1β levels exacerbates extended cognitive dysfunction following severe inflammation in C57/BL6 mice. • TRPM2 serves as a mediator of IL-1β's impact on the persistent cognitive impairment resulting from severe inflammation in C57/BL6. • IL-1β expedites astrocyte apoptosis by upregulating TRPM2 activity. Sepsis could lead to chronic cognitive impairment by unclear molecular mechanisms. Transient receptor potential melastatin-2 (TRPM2) is essential against immunity-related activities and inflammation. Our study attempted to decipher the relationship between cognitive impairment caused by severe inflammation and TRPM2 expression levels. Severe inflammation was induced by intraperitoneally injecting C57/BL6 mice with a high dosage (5 mg kg−1) of Lipopolysaccharide (LPS). Fear conditioning and a Morris water maze test were performed to examine the cognitive abilities of the mice. Moreover, the signaling and expression of pro-inflammatory cytokines and TRPM2 were measured using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry and immunofluorescence staining helped to determine the astrocyte apoptosis rate. Severe inflammation can lead to long-term cognitive impairment in C57/BL6 mice. The interleukin-1 beta (IL-1β) levels intra-hippocampus were significantly elevated until P14 post-LPS introduction. At both P7 and P14, there is an up-regulation of TRPM2 expression within hippocampus. Administration of recombinant IL-1β to astrocytes results in a significant up-regulation of TRPM2 expression. IL-1β or TRPM2 level knockdown helped counter the cognitive impairment caused by significant inflammation. A continuous increase in IL-1β levels within the hippocampus can lead to cognitive impairment by enhancing TRPM2 levels caused by severe inflammation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *COGNITION disorders
*LABORATORY mice
*TRP channels
Subjects
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 128
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 175242341
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.111380