Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring
IntroductionBrain development involves several critical stages, such as proliferation, neuronal migration, axonal pathfinding, and connection formation. Sevoflurane, a γ-aminobutyric acid (GABA) receptor agonist, is widely used as an inhaled general anesthetic. However, its impact on brain developme...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1556703/full |
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| author | Tianyuan Wang Tianyuan Wang Huandi Weng Yalan Li |
| author_facet | Tianyuan Wang Tianyuan Wang Huandi Weng Yalan Li |
| author_sort | Tianyuan Wang |
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| description | IntroductionBrain development involves several critical stages, such as proliferation, neuronal migration, axonal pathfinding, and connection formation. Sevoflurane, a γ-aminobutyric acid (GABA) receptor agonist, is widely used as an inhaled general anesthetic. However, its impact on brain development has raised increasing concerns, particularly regarding prenatal exposure. This study aims to investigate the effects of prenatal sevoflurane exposure (PSE) at different cortical stages, focusing on its impact on the migration of glutamatergic and GABAergic neurons and neuronal behavior in offspring.MethodsPSE was administered at two critical prenatal stages: embryonic day (E) 12.5 and E18.5. Double in situ hybridization was used to identify the coexpression of GABA receptors in Pax6- and Mash1-positive cells in the forebrain. The radial migration of glutamatergic neurons and the tangential migration of GABAergic neurons were analyzed. Behavioral tests, including the open-field test, elevated plus-maze test, forced swim test, tail suspension test, sucrose preference test, and Morris water maze, were performed on offspring to assess anxiety-like behaviors, depression, and learning and memory impairments.ResultsPSE inhibits the radial migration of glutamatergic neurons and promotes the tangential migration of GABAergic neurons. Specifically, early exposure (E12.5) inhibited the expression of the Pax6–Tbr2–Tbr1 cascade and the radial migration of Tbr1 in the ventral prefrontal cortex (PFC), whereas late exposure (E18.5) inhibited this process on the dorsal side. In addition, offspring mice with PSE exhibited increased anxiety-like behaviors, rather than depression, as demonstrated by reduced time spent in the center of the open-field test and in the open arms of the elevated plus-maze test. No significant differences were observed in the forced swim test, tail suspension test, or sucrose preference test. Furthermore, learning and memory impairments were observed in the Morris water maze.ConclusionOur results indicate that PSE at E12.5 and E18.5 leads to abnormalities in the migration of glutamatergic and GABAergic neurons, affecting long-term anxiety-like behaviors and causing learning and memory impairments in offspring mice. |
| format | Article |
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| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-e12b0f1d1a614f368e01a09416bd437f2025-08-20T01:55:12ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-04-011910.3389/fnins.2025.15567031556703Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspringTianyuan Wang0Tianyuan Wang1Huandi Weng2Yalan Li3School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaIntroductionBrain development involves several critical stages, such as proliferation, neuronal migration, axonal pathfinding, and connection formation. Sevoflurane, a γ-aminobutyric acid (GABA) receptor agonist, is widely used as an inhaled general anesthetic. However, its impact on brain development has raised increasing concerns, particularly regarding prenatal exposure. This study aims to investigate the effects of prenatal sevoflurane exposure (PSE) at different cortical stages, focusing on its impact on the migration of glutamatergic and GABAergic neurons and neuronal behavior in offspring.MethodsPSE was administered at two critical prenatal stages: embryonic day (E) 12.5 and E18.5. Double in situ hybridization was used to identify the coexpression of GABA receptors in Pax6- and Mash1-positive cells in the forebrain. The radial migration of glutamatergic neurons and the tangential migration of GABAergic neurons were analyzed. Behavioral tests, including the open-field test, elevated plus-maze test, forced swim test, tail suspension test, sucrose preference test, and Morris water maze, were performed on offspring to assess anxiety-like behaviors, depression, and learning and memory impairments.ResultsPSE inhibits the radial migration of glutamatergic neurons and promotes the tangential migration of GABAergic neurons. Specifically, early exposure (E12.5) inhibited the expression of the Pax6–Tbr2–Tbr1 cascade and the radial migration of Tbr1 in the ventral prefrontal cortex (PFC), whereas late exposure (E18.5) inhibited this process on the dorsal side. In addition, offspring mice with PSE exhibited increased anxiety-like behaviors, rather than depression, as demonstrated by reduced time spent in the center of the open-field test and in the open arms of the elevated plus-maze test. No significant differences were observed in the forced swim test, tail suspension test, or sucrose preference test. Furthermore, learning and memory impairments were observed in the Morris water maze.ConclusionOur results indicate that PSE at E12.5 and E18.5 leads to abnormalities in the migration of glutamatergic and GABAergic neurons, affecting long-term anxiety-like behaviors and causing learning and memory impairments in offspring mice.https://www.frontiersin.org/articles/10.3389/fnins.2025.1556703/fullprenatal sevoflurane exposureneuronal migrationembryonic cortical development stageneurotoxicityGABA |
| spellingShingle | Tianyuan Wang Tianyuan Wang Huandi Weng Yalan Li Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring Frontiers in Neuroscience prenatal sevoflurane exposure neuronal migration embryonic cortical development stage neurotoxicity GABA |
| title | Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| title_full | Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| title_fullStr | Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| title_full_unstemmed | Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| title_short | Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| title_sort | comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring |
| topic | prenatal sevoflurane exposure neuronal migration embryonic cortical development stage neurotoxicity GABA |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1556703/full |
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