Abstract
Rationale
Due to its anti-inflammatory effect, dexmedetomidine (DEX) can confer neuroprotection in postoperative neurocognitive disorders (NCD). Here, the mechanism responsible for this effect of DEX is rarely ascertained.
Objectives
Our research was implemented to figure out mechanism governing the protection of DEX against hippocampal neuroinflammation in postoperative NCD.
Methods
Exploratory laparotomy was applied for generating a postoperative NCD mouse model before bilateral hippocampal injection with microRNA (miR)-329-3p-agomir and intraperitoneal injection with DEX. Cognitive function of mice was evaluated by water maze test and fear conditioning test. Immunofluorescence was performed to assess microglial activation in hippocampus. After cell transfection and DEX treatment, mouse microglial cells (BV-2) were stimulated by lipopolysaccharide (LPS). IL-1β, IL-6, and TNF-α levels and the number of phagocytes were assessed by ELISA and flow cytometry. Dual-luciferase reporter assay was adopted to assess the relationship between miR-329-3p and CREB1.
Results
miR-329-3p expression was reduced in the postoperative NCD mice after DEX treatment. DEX treatment or miR-329-3p downregulation caused attenuated cognitive dysfunction and microglia activation as well as reduced IL-1β, IL-6, and TNF-α levels in the hippocampus of the postoperative NCD mice. Mechanistically, miR-329-3p inversely targeted CREB1 that activated IL1RA in LPS-induced BV-2 cells. DEX treatment, miR-329-3p inhibition, or CREB1 or IL1RA upregulation curtailed the release of proinflammatory proteins and the number of phagocytes in LPS-induced BV-2 cells.
Conclusions
Collectively, our data provided the novel insight of the neuroprotective mechanism of DEX in postoperative NCD pertaining to the miR-329-3p/CREB1/IL1RA axis.
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Data availability
The datasets generated/analyzed during the current study are available.
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JQC and XXJ designed the study. YTZ and ZZS collated the data, carried out data analyses, and produced the initial draft of the manuscript. JZ contributed to drafting the manuscript. QD and BRW contributed to revising the manuscript. All authors have read and approved the final submitted manuscript.
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Chen, J., Ding, Q., Jiao, X. et al. Dexmedetomidine attenuates hippocampal neuroinflammation in postoperative neurocognitive disorders by inhibiting microRNA-329-3p and activating the CREB1/IL1RA axis. Psychopharmacology 239, 2171–2186 (2022). https://doi.org/10.1007/s00213-022-06091-y
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DOI: https://doi.org/10.1007/s00213-022-06091-y