Related Experiment Video
Updated: May 11, 2025
Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain
Tianyuan Wang1,2, Huandi Weng3, Yalan Li2
1School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, China.
Insights
Prenatal sevoflurane exposure (PSE) disrupts brain development by altering neuronal migration, leading to anxiety and impaired learning and memory in offspring. This study highlights critical developmental windows affected by anesthetic exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Brain development involves critical stages like neuronal migration.
- Sevoflurane, a common anesthetic, is a gamma-aminobutyric acid (GABA) receptor agonist.
- Prenatal exposure to anesthetics raises concerns about neurodevelopmental outcomes.
Purpose of the Study:
- To investigate the effects of prenatal sevoflurane exposure (PSE) on neuronal migration.
- To examine the impact of PSE at different embryonic stages (E12.5 and E18.5) on glutamatergic and GABAergic neurons.
- To assess the long-term behavioral consequences, including anxiety and cognitive function, in offspring.
Main Methods:
- Administered PSE at embryonic day 12.5 and 18.5 in mice.
- Analyzed neuronal migration patterns using double in situ hybridization.
- Conducted a battery of behavioral tests to evaluate anxiety, depression, learning, and memory.
Main Results:
- PSE inhibited radial migration of glutamatergic neurons and promoted tangential migration of GABAergic neurons.
- Early PSE (E12.5) affected ventral prefrontal cortex development, while late PSE (E18.5) affected dorsal PFC development.
- Offspring exhibited increased anxiety-like behaviors and significant learning and memory impairments.
Conclusions:
- Prenatal sevoflurane exposure at critical developmental stages disrupts neuronal migration.
- PSE leads to lasting neurodevelopmental deficits, including anxiety and cognitive impairments.
- These findings underscore the potential risks of anesthetic exposure during sensitive prenatal periods.
Introduction:
Brain 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.
Methods:
PSE 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.
Results:
PSE 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.
Conclusion:
Our 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.
