title: Multiple sevoflurane anesthesia in pregnant mice inhibits neurogenesis of fetal hippocampus via repressing transcription factor Pax6.
abstract: Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5%×2h and 4.1%×2h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze. The expression of Ccnd1 and Pax6 in fetal brains and NSCs were analyzed by immunofluorescence, Western blot and qPCR. The neurogenesis was evaluated by BrdU staining. Results showed that multiple sevoflurane exposure in pregnant mice caused the decrease of Pax6 and Ccnd1 expression, the inhibition of NSCs proliferation and fetal hippocampus neurogenesis, which may contribute to the impaired learning and memory in offspring at P28. Moreover, lithium mitigated the sevoflurane-induced reduction in Pax6, Ccnd1 and neurogenesis. All these results suggest that multiple sevoflurane exposure may induce detrimental effects in the developing brains of fetus and offspring by the depression of neurogenesis through Pax6 pathway.
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ling
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Zhanggang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China. Electronic address: cangjing_zs@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Cang
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D007858:Learning / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects*; D008568:Memory / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D000071841:PAX6 Transcription Factor / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000077149:Sevoflurane
chemical_list: C530105:Ccnd1 protein, mouse; D008738:Methyl Ethers; D000071841:PAX6 Transcription Factor; C000605732:Pax6 protein, mouse; D019938:Cyclin D1; D000077149:Sevoflurane
keywords: Ccnd1; Cognitive function; Lithium; Neurogenesis; Pax6; Sevoflurane