Ganglioside GM1 Alleviates Propofol-Induced Pyroptosis in the Hippocampus of Developing Rats via the PI3K/AKT/NF-κB Signaling Cascade

• Published in: International journal of molecular sciences 2024-12, Vol.25 (23), p.12662
• Main Authors: Zhang, Zhiheng, Du, Shan, Chen, Xinzhang, Qiu, Di, Li, Siyao, Han, Lin, Bai, Hui, Gao, Ruifeng
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Brain; Brain research; Cell death; Cognition disorders; Cognitive ability; Cytokines; Enzyme-linked immunosorbent assay; G(M1) Ganglioside - metabolism; G(M1) Ganglioside - pharmacology; Gangliosides; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Male; Neurodegeneration; Neuroprotective Agents - pharmacology; Neurotoxicity; NF-kappa B - metabolism; PC12 Cells; Pediatrics; Phenols; Phosphatidylinositol 3-Kinases - metabolism; Propofol; Propofol - pharmacology; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Pyroptosis - drug effects; Rats; Rats, Sprague-Dawley; Signal transduction; Signal Transduction - drug effects; Traumatic brain injury
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252312662

In pediatric and intensive care units, propofol is widely used for general anesthesia and sedation procedures as a short-acting anesthetic. Multiple studies have revealed that propofol causes hippocampal injury and cognitive dysfunction in developing animals. As is known, GM1, a type of ganglioside, plays a crucial role in promoting nervous system development. Consequently, this study explored whether GM1 mitigated neurological injury caused by propofol during developmental stages and investigated its underlying mechanisms. Seven-day-old SD rats or PC12 cells were used in this study for histopathological analyses, a Morris water maze test, a lactate dehydrogenase release assay, Western blotting, and an ELISA. Furthermore, LY294002 was employed to explore the potential neuroprotective effect of GM1 via the PI3K/AKT signaling cascade. The results indicated that GM1 exerted a protective effect against hippocampal morphological damage and pyroptosis as well as behavioral abnormalities following propofol exposure by increasing p-PI3K and p-AKT expression while decreasing p-p65 expression in developing rats. Nevertheless, the inhibitor LY294002, which targets the PI3K/AKT cascade, attenuated the beneficial effects of GM1. Our study provides evidence that GM1 confers neuroprotection and attenuates propofol-induced developmental neurotoxicity, potentially involving the PI3K/AKT/NF-κB signaling cascade.