Inhibition of the P38 MAPK/NLRP3 pathway mitigates cognitive dysfunction and mood alterations in aged mice after abdominal surgery plus sevoflurane.

BACKGROUND: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model. METHODS: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3ß (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed. RESULTS: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors. CONCLUSIONS: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

[Advances on olfactory receptor gene].

The olfactory sense plays a key role in animals'life time. The main gene related with olfaction was olfactory receptor (OR) gene. This review introduced the structure, expression regulation, distribution, molecular evolution and polymorphism of OR gene. The relationship between OR gene and olfactory function and olfactory deficits was also discussed.

Exploration of mtDNA control region sequences in Chinese Tibetan Mastiffs.

The control region of mitochondrial DNA (mtDNA) was obtained from 40 purebred Chinese Tibetan Mastiffs (TMs). Sequence structure and genetic diversity were analyzed, and a phylogenetic tree was constructed. The TM mtDNA control region was composed of ETAS (extended termination associated sequences), CD (a central domain) and CSBs (conserved sequenced blocks) and sequence length showed some diversity, which was mainly caused by the number of 10 nucleotide repeat units [5'-GTA CAC GT (G/A) C-3'] between CSB I and CSB II, which ranged from 27 to 35 among individuals. Seventy-five polymorphic sites were identified, which defined 37 haplotypes; the haplotype diversity was 0.990, and the nucleotide diversity was 1.201. Based on the control region sequences, Chinese TMs were divided into three categories, which were consistent with the origin and geographical classification of TMs. Phylogenetic analysis of 538-bp HVR-I sequences revealed that TMs were most closely related to Labrador Retrievers.