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Ganglioside GM1 Alleviates Propofol-Induced Pyroptosis in the Hippocampus of Developing Rats via the PI3K/AKT/NF-κB
Zhiheng Zhang1,2,3, Shan Du1,2, Xinzhang Chen3
1College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China.
Insights
Ganglioside GM1 protects developing brains from propofol-induced injury. This study shows GM1 mitigates hippocampal damage and cognitive deficits by modulating the PI3K/AKT/NF-κB pathway.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Propofol is a common anesthetic in pediatric intensive care.
- Propofol exposure can cause hippocampal injury and cognitive dysfunction in developing animals.
- Ganglioside GM1 is vital for nervous system development.
Purpose of the Study:
- To investigate if GM1 mitigates propofol-induced neurological injury in developing rats.
- To elucidate the underlying mechanisms of GM1's neuroprotective effects.
Main Methods:
- Utilized 7-day-old Sprague-Dawley rats and PC12 cells.
- Performed histopathological analyses, Morris water maze test, LDH release assay, Western blotting, and ELISA.
- Investigated the PI3K/AKT signaling pathway using the inhibitor LY294002.
Main Results:
- GM1 protected against propofol-induced hippocampal damage, pyroptosis, and behavioral deficits.
- GM1 increased p-PI3K and p-AKT expression while decreasing p-p65 expression.
- The PI3K/AKT inhibitor LY294002 reversed the beneficial effects of GM1.
Conclusions:
- GM1 confers neuroprotection against propofol-induced developmental neurotoxicity.
- The protective effects of GM1 involve the PI3K/AKT/NF-κB signaling cascade.
Abstract:
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.
