title: Selective regulation of neurosteroid biosynthesis under ketamine-induced apoptosis of cortical neurons in vitro.
abstract: Numerous studies have suggested that ketamine administration can induce neuroapoptosis in primary cultured cortical neurons. Neurosteroids modulate neuronal function and serve important roles in the central nervous system, however the role of neurosteroids in neuroapoptosis induced by ketamine remains to be elucidated. The present study aimed to explore whether neurosteroidogenesis was a pivotal mechanism for neuroprotection against ketamine-induced neuroapoptosis, and whether it may be selectively regulated under ketamine-induced neuroapoptosis conditions in primary cultured cortical neurons. To study this hypothesis, the effect of ketamine exposure on neurosteroidogenesis in primary cultured cortical neurons was investigated. Cholesterol, a substrate involved in the synthesis of neurosteroids, was added to the culture medium, and neurosteroids were quantified using high-performance liquid chromatography-tandem mass spectrometry analysis. The data demonstrated that cholesterol blocked ketamine-induced neuroapoptosis by promoting the synthesis of various neurosteroids, and the pathway of neurosteroid testosterone conversion into estradiol was inhibited by ketamine exposure. These data suggest that endogenous neurosteroids biosynthesis is critical for neuroprotection against ketamine-induced neuroapoptosis and inhibiting the biosynthesis of neuroprotective-neurosteroid estradiol is of notable importance for ketamine-induced neuroapoptosis.
authors.affiliation: Department of Anesthesiology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese People's Liberation Army, Shijiazhuang, Hebei 050082, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Gynecology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese People's Liberation Army, Shijiazhuang, Hebei 050082, P.R. China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese People's Liberation Army, Shijiazhuang, Hebei 050082, P.R. China.
authors.forename: Gai
authors.initials: G
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, Bethune International Peace Hospital of Chinese People's Liberation Army, Shijiazhuang, Hebei 050082, P.R. China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002784:Cholesterol / Q000008:administration & dosage; D007649:Ketamine / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D007649:Ketamine; D002784:Cholesterol