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Methodology for the Study of Learning and Memory in Juvenile Rats Using Sevoflurane Anesthesia to Assess Hippocampal
Ye Jiang1, Lai Jiang1, Guohui Li2
1Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.
Insights
Sevoflurane temporarily impairs memory retention in juvenile rats, decreasing p-CREB and c-fos expression in the hippocampus. This effect is short-term and not dependent on dosing frequency.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Cognitive impairments during brain development are challenging to study due to neurodevelopmental dynamics and methodological limitations.
- Sevoflurane, a common anesthetic, may impact cognitive functions in developing brains.
- Understanding the molecular mechanisms, such as the NMDAR/p-CREB/c-fos pathway, is crucial for assessing these effects.
Purpose of the Study:
- To investigate the impact of sevoflurane on cognitive impairments in the developing brain of juvenile rats.
- To examine the effects of sevoflurane on memory retention and the expression of p-CREB and c-fos in hippocampal neurons.
- To explore the role of the NMDAR/p-CREB/c-fos signaling pathway in sevoflurane-induced cognitive deficits.
Main Methods:
- Utilized a Y-maze test to assess learning and memory retention in juvenile rats exposed to sevoflurane.
- Employed immunohistochemistry to quantify p-CREB and c-fos positive neurons in hippocampal tissue.
- Compared outcomes across five groups: normal, 60% O2, sham training, single-dose sevoflurane, and multiple-dose sevoflurane, with varying sacrifice times.
Main Results:
- Sevoflurane exposure significantly decreased memory retention in juvenile rats compared to the control group (60% O2).
- A notable reduction in p-CREB and c-fos expression was observed in hippocampal neurons of rats exposed to sevoflurane.
- These cognitive and molecular effects were primarily short-term, with no significant long-term impact observed 30 days post-exposure or based on dosing frequency.
Conclusions:
- Sevoflurane exhibits a short-term negative effect on memory maintenance in juvenile rats.
- The anesthetic agent reduces the expression of key proteins (p-CREB and c-fos) involved in memory formation within the hippocampus.
- The study highlights the transient nature of sevoflurane's impact on cognitive function and neuronal expression in the developing brain.
Abstract:
Studying cognitive impairments during brain development faces challenges due to the dynamic nature of neurodevelopment, methodological constraints, and contextual barriers. This study investigated an integrated methodological approach to study cognitive impairments in the developing brain caused by sevoflurane based on memory and p-CREB and c-fos expression in hippocampal neurons through the NMDAR/p-CREB/c-fos signaling pathway in juvenile rats. Sixty-four 21-day-old SD male rats (body weight <80 g) were divided into five groups: normal (n=8), 60% O2 (n=16), sham training (n=8), single-dose sevoflurane (n=16), and multiple-dose sevoflurane (n=16). The two sevoflurane groups were sub-grouped into sacrifice 1 day (groups sev1a and sev1b) and 30 days (groups sev30a and sev30b) after training (n=8/subgroup); all other rats were sacrificed 1 h after training. The Y-maze test was used to evaluate learning and memory retention. Immunohistochemistry was used to determine the number of p-CREB- and c-fos-positive neurons in the hippocampus specimens. Compared with the 60% O2 group (memory retention of 86.33% ± 17.52%), the memory of rats in the sev1a and sev1b groups showed a significant decrease (sev1a: 44.29% ± 11.26%; sev1b: 62.42% ± 7.27%; all P<0.05), while the sev1b and sev30b groups showed no significant differences (sev30a: 84.41% ± 14.15%; sev30b: 85.21% ± 11.61%; all P>0.05). Compared with the 60% O2 group (c-fos: 92.83 ± 7.88; p-CREB: 72.22 ± 8.89), the expression of p-CREB and c-fos in hippocampal neurons decreased in the sev1a group (c-fos: 23.13 ± 3.28; p-CREB: 22.88 ± 5.18) and the sev30 group (c-fos: 23.22 ± 3.13; p-CREB: 25.58 ± 2.26) (all P<0.05), while the sev30a and sev30b groups showed no significant differences (all P>0.05). Sevoflurane has a short-term negative stimulating effect on the memory maintenance ability of juvenile rats without an impact based on dosing frequency. Sevoflurane decreases the expression of p-CREB and c-fos in hippocampal neurons of juvenile rats.
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