Protective Effect of GM1 Attenuates Hippocampus and Cortex Apoptosis After Ketamine Exposure in Neonatal Rat via PI3K/AKT/GSK3ß Pathway.
Mol Neurobiol
; 58(7): 3471-3483, 2021 Jul.
Article
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| MEDLINE
| ID: mdl-33733293
Ketamine is a widely used analgesic and anesthetic in obstetrics and pediatrics. Ketamine is known to promote neuronal death and cognitive dysfunction in the brains of humans and animals during development. Monosialotetrahexosyl ganglioside (GM1), a promoter of brain development, exerts neuroprotective effects in many neurological disease models. Here, we investigated the neuroprotective effect of GM1 and its potential underlying mechanism against ketamine-induced apoptosis of rats. Seven-day-old Sprague Dawley (SD) rats were randomly divided into the following four groups: (1) group C (control group: normal saline was injected intraperitoneally); (2) group K (ketamine); (3) group GM1 (GM1 was given before normal saline injection); and (4) GM1+K group (received GM1 30 min before continuous exposure to ketamine). Each group contained 15 rats, received six doses of ketamine (20 mg/kg), and was injected with saline every 90 min. The Morris water maze (MWM) test, the number of cortical and hippocampal cells, apoptosis, and AKT/GSK3ß pathway were analyzed. To determine whether GM1 exerted its effect via the PI3K/AKT/GSK3ß pathway, PC12 cells were incubated with LY294002, a PI3K inhibitor. We found that GM1 protected against ketamine-induced apoptosis in the hippocampus and cortex by reducing the expression of Bcl-2 and Caspase-3, and by increasing the expression of Bax. GM1 treatment increased the expression of p-AKT and p-GSK3ß. However, the anti-apoptotic effect of GM1 was eliminated after inhibiting the phosphorylation of AKT. We showed that GM1 lessens ketamine-induced apoptosis in the hippocampus and cortex of young rats by regulating the PI3K/AKT/GSK3ß pathway. Taken together, GM1 may be a potential preventive treatment for the neurotoxicity caused by continuous exposure to ketamine.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
Fosfatidilinositol 3-Quinasas
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Proteínas Proto-Oncogénicas c-akt
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Glucógeno Sintasa Quinasa 3 beta
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Gangliósido G(M1)
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Hipocampo
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Ketamina
Límite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos