Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

Formyl peptide receptor-2 (FPR2) belongs to the G protein-coupled receptor (GPCR) family and plays a critical role in the development of various tumors. However, the roles and mechanisms of FPR2 in glioblastoma (GBM) remain poorly understood. In this study, we observed significant upregulation of FPR2 in glioma cell lines and tissues, and elevated FPR2 expression levels are correlated with poor patient survival. Furthermore, we found that FPR2 suppresses the autophagy mediated by BECN1 and ATG5 in GBM cells. Using Western blot analysis, we revealed that FPR2 regulates GBM cell invasion via the PI3K/AKT signaling pathway. Additionally, we demonstrated that knocking down FPR2 expression in GBM cells reduced tumor cell migration and invasion in vitro and tumor growth in vivo. The inhibition of FPR2 led to cell cycle arrest at the G2/M phase and increased apoptosis. Finally, our findings indicate that FPR2 may prevent autophagy-induced epithelial‒mesenchymal transition (EMT)-like changes by preventing autophagy-induced degradation of Snail. Our findings suggest that FPR2 promotes GBM cell migration and invasion through the inhibition of autophagy and the activation of the PI3K/AKT signaling pathway, highlighting the potential of inducing autophagy as a therapeutic approach to inhibit invasion in GBM with high FPR2 expression.

Repetitive traumatic brain injury (RTBI) refers to brain injuries resulting from an external mechanical force causing cumulative and frequently severe neurological consequences. This study aimed to explore the neuroprotective effect of alogliptin (ALO) on RTBI-provoked endoplasmic reticulum (ER) stress and investigate the potential underlying mechanisms. For RTBI induction, rats were exposed to a sharp-edged weight at the right interior frontal area of the right cortex, one drop per day for five successive days. ALO (20 mg/kg/day, p.o.) was administered for one week. Results depicted that ALO recovered motor abnormalities and enhanced motor coordination in the open field test, decreased immobility and increased climbing time in the forced swimming test, and corrected histological aberrations. Moreover, ALO counteracted RTBI-triggered ER stress via suppression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), aggregation of β-amyloid and Tau proteins, as well as elevation of the cortical content of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrKB). ALO also exhibited an antioxidant and anti-inflammatory potential in addition to its effect on the gene expression of miRNAs (miRNA-322 and miRNA-125b). In conclusion, ALO exhibited a neuroprotective effect by mitigating ER stress induced in an RTBI rat model.

Sevoflurane (Sevo) anaesthesia in children is linked to an increased incidence of postoperative emergence agitation (EA) and potential neurotoxicity in developing brains. However, the specific risks of subanaesthetic foetal or neonatal exposure to Sevo remain unclear. This study evaluates the safety and efficacy of combining dexmedetomidine (Dex) with Sevo to manage EA in paediatric anaesthesia. A systematic review and meta-analysis of randomized controlled clinical trials involving children under 8 years old revealed that Dex significantly reduces EA incidence when administered via intravenous, perineural, and intranasal routes. Using in utero electroporation, we found that pregnant mice exposed to 2.5% Sevo at embryonic days 14.5 and 15.5 exhibited transient neuronal migration deficits, with 25% of neurons delayed in deeper cortical layers. However, these neurons migrated to the cortex by postnatal day 8. Neonatal mice exposed to 2.5% Sevo experienced a 10% reduction in dendritic spine density in adolescence, associated with impaired somatosensory function, as assessed by the Von Frey test. Remarkably, Dex pretreatment ameliorated these pathological and functional changes. Thus, foetal or neonatal Sevo exposure can delay neuronal migration and reduce dendritic spine density. Dex co-administration effectively mitigates these adverse outcomes, supporting its potential use in paediatric anaesthesia to protect developing brains.