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Effect of multiple neonatal sevoflurane exposures on hippocampal apolipoprotein E levels and learning and memory
Junli Jiang1, Chunchun Tang2, Juanjuan Ren1
1Guizhou Key Laboratory of Basic Research of Anesthesia and Organ Protection, Zunyi 563000, Guizhou, PR China.
Insights
Early sevoflurane exposure in young rats reduced hippocampal volume and increased ApoE expression, impacting cognitive function. These effects were regionally specific and reversible in adulthood.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Sevoflurane anesthesia is commonly used in pediatric patients.
- Neonatal exposure to anesthetics may affect brain development and cognitive function.
- The impact of early sevoflurane exposure on hippocampal ApoE expression is not fully understood.
Purpose of the Study:
- To investigate the long-term effects of early multiple sevoflurane exposures on cognitive function.
- To determine if sevoflurane exposure alters hippocampal ApoE expression later in development.
- To assess changes in hippocampal volume following early sevoflurane exposure.
Main Methods:
- Sprague-Dawley rats were exposed to sevoflurane at postnatal days 7, 14, and 21.
- Learning and memory were evaluated using the Morris water maze.
- Hippocampal volume was measured via MRI.
- Hippocampal ApoE expression was analyzed using immunohistochemistry and PCR.
Main Results:
- Sevoflurane exposure led to decreased learning and memory abilities, though not statistically significant.
- Significant reductions in hippocampal volume and length were observed in young and adult sevoflurane-exposed rats.
- ApoE expression and mRNA levels were significantly elevated in the hippocampus of young exposed rats, but normalized in adults.
Conclusions:
- Neonatal sevoflurane exposure can decrease hippocampal volume and increase ApoE expression.
- The observed changes in ApoE expression are region-specific within the hippocampus.
- These alterations in ApoE expression appear to be reversible by adulthood.
Background:
Sevoflurane anesthesia is widely used in pediatric patients. In this study, we investigated whether early multiple exposures to sevoflurane induced cognitive dysfunction by altering the hippocampal expression of ApoE later in development.
Methods:
Sprague-Dawley rats were exposed to 2.6% sevoflurane at postnatal day 7 (P7), P14, and P21 for 2 h. The ability of learning and memory was assessed using the Morris water maze at P37 and P97. The hippocampal volume was measured by magnetic resonance imaging (MRI) at P37 and P97. The hippocampal expression of ApoE was assessed by immunohistochemical analyses and real-time polymerase chain reaction (PCR).
Results:
Behavioral testing revealed that the ability of learning and memory in the sevoflurane-exposed rats was decreased compared with the control animals; however, there was no significant difference (P > 0.05). The MRI results showed a significant decrease in the left hippocampal volume, left maximum hippocampal length, and right maximum hippocampal length in the sevoflurane young group compared with the control young group (P < 0.05). The brain volume, left maximum hippocampal length, right hippocampal volume, and maximum brain length were significantly lower in the sevoflurane adult group than in the control adult group (P < 0.05). In young animals, the ApoE expression in the hippocampal CA1 and CA3 regions and the ApoE mRNA level were significantly higher compared with the control group (P < 0.05), but not in the dentate gyrus region (P > 0.05). Among the adult animals, there was no significant difference between the groups in any parameter tested (P > 0.05).
Conclusion:
Multiple exposures to sevoflurane during the neonatal period decreased the volume of the hippocampus and increased the hippocampal expression of ApoE. The differential expression level of ApoE in different hippocampal subdivisions suggested that the expression of ApoE was regionally specific and reversible.
