Department of Anesthesiology and Perioperative Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Henan International Joint Laboratory of Anesthesiology and Perioperative Cognitive Function, Zhengzhou, Henan, China.
Mol Neurobiol. 2022 May;59(5):2799-2807. doi: 10.1007/s12035-021-02629-x. Epub 2022 Feb 24.
It remains unclear whether exposure to sevoflurane produces different effects on long-term cognitive function in developing and mature brains. In the present study, Sprague-Dawley neonatal rats at postnatal day (PND) 7 and adult rats (PND 56) were used in all experiments. We performed fear conditioning testing to examine long-term fear memory following 4-h sevoflurane exposure. We assessed hippocampal synapse ultrastructure with a transmission electron microscope. Moreover, we investigated the effect of sevoflurane exposure on the expression of postsynaptic protein 95 (PSD-95) and its binding protein kalirin-7 in the hippocampus. We observed that early exposure to sevoflurane in neonatal rats impairs hippocampus-dependent fear memory, reduces hippocampal synapse density, and dramatically decreases the expressions of PSD-95 and kalirin-7 in the hippocampus of the developing brain. However, sevoflurane exposure in adult rats has no effects on hippocampus-dependent fear memory and hippocampal synapse density, and the expressions of PSD-95 and kalirin-7 in the adult hippocampus are not significantly altered following sevoflurane treatment. Our results indicate that sevoflurane exposure produces differential effects on long-term fear memory in neonatal and adult rats and that PSD-95 signaling may be involved in the molecular mechanism for early sevoflurane exposure-caused long-term fear memory impairment.
目前尚不清楚七氟醚暴露是否会对发育中和成熟大脑的长期认知功能产生不同的影响。在本研究中，所有实验均使用了新生大鼠（出生后第 7 天，PND7）和成年大鼠（PND56）。我们进行了恐惧条件反射测试，以检测 4 小时七氟醚暴露后长期的恐惧记忆。我们使用透射电子显微镜评估海马突触超微结构。此外，我们研究了七氟醚暴露对海马中突触后蛋白 95（PSD-95）及其结合蛋白 kalirin-7 表达的影响。我们观察到，新生大鼠早期暴露于七氟醚会损害海马依赖的恐惧记忆，降低海马突触密度，并显著降低发育中大脑中海马中 PSD-95 和 kalirin-7 的表达。然而，成年大鼠暴露于七氟醚对海马依赖的恐惧记忆和海马突触密度没有影响，并且七氟醚处理后成年海马中 PSD-95 和 kalirin-7 的表达没有明显改变。我们的研究结果表明，七氟醚暴露对新生和成年大鼠的长期恐惧记忆产生不同的影响，PSD-95 信号可能参与了早期七氟醚暴露引起的长期恐惧记忆损伤的分子机制。
