Abstract:Objective: To explore the effect of sevoflurane anesthesia on dendritic spine development in late pregnant rat offspring and its mechanism. Methods: Pregnant rats were divided into control group, sevoflurane-1h group, sevoflurane-3h group and sevoflurane-6h group, they were anesthetized with 2.3% sevoflurane respectively. P31 offspring rats were subjected to water maze test and executed with high CO2 concentration. Brain tissue was taken for electrophysiological experiments to detect long duration enhancement in CA1 region of hippocampus, Golgi staining to assess dendritic spine status and western blot to detect BDNF/TrkB protein expression.Results: Compared to the control group, the latency to evade was not altered in the water maze experiment in late pregnant rat offspring P35 pups anesthetized with sevoflurane for 1h, whereas the latency to evade increased significantly in the sevoflurane-3h and sevoflurane-6h groups, and the number of platform crossings and quadrant III dwell time decreased significantly. In addition, sevoflurane anesthesia at 3h and 6h caused a significant decrease in the slope of fEPSP and a significant decrease in the density and length of dendritic spines in the pups, however, there was no effect on the fEPSP and dendritic spine status in the sevoflurane-1h group. At the same time, the expression of PSD-95, BDNF and p-TrkB in hippocampal tissues of young rats was significantly reduced by 3h and 6h sevoflurane anesthesia.Conclusion: The reduced learning and memory capacity in late pregnant rat pups after prolonged anaesthesia is caused by reduced BDNF expression, which results from reduced p-TrkB expression mediating reduced PSD-95 protein, leading to impaired dendritic spine development.
苏娟, 张振忠, 张友佳. 七氟醚基于BDNF/TrkB信号通路对孕晚期大鼠子代树突棘发育的影响[J]. 河北医学, 2022, 28(4): 567-571.
SU Juan, et al. Effect of Sevoflurane Based on BDNF/TrkB Signaling Pathway on Dendritic Spine Development in Rat Offspring During Late Pregnancy. HeBei Med, 2022, 28(4): 567-571.
[1] hung W,Yoon S,Shin YS.Multiple exposures of sevoflurane during pregnancy induces memory impairment in young female offspring mice[J].Korean Anesthesiol,2017,70(6):642~647. [2] Zhang Y,Tian SY,Li YW,et al.Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway[J].Gene,2015,569(1):60~75. [3] Wu XY,Zhang YL,Xia HL,et al.LIMK1 attenuates sevoflurane-induced neurodevelopmental toxicity through caspase-3/ cofilin/PARP-1 pathway[J].Biol Regul Homeost Agents,2020,34(5):1923~1928. [4] Boros B D,Greathouse K M,Gentry E G,et al.Dendritic spines provide cognitive resilience against Alzheimer's disease[J].Ann Neurol,2017,82(4):602~614. [5] Zhu L,Yang L,Zhao X M,et al.Xanthoceraside modulates NR2B-containing NMDA receptors at synapses and rescues learning-memory deficits in APP/PS1 transgenic mice[J].Psychopharmacology,2018,235(1):337~349. [6] Poppe L,Rue,Timmers M,et al.LEphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer's disease[J].Alzheimers Res Ther,2019,11(1):1~13. [7] Le Y,Liu S,Peng M,et al.Aging differentially affects the loss of neuronal dendritic spine,neuroinflammation and memory impairment at rats after surgery[J].PLoS One,2014,9(9):e106837. [8] Eilam-Stock T,Serrano P,Frankfurt M,et al.Bisphenol-A impairs memory and reduces dendritic spine density in adult male rats[J].Behav Neurosci,2012,126(1):175~185. [9] Iryna H,Pirta H.Chemical LTD,but not LTP,induces transient accumulation of gelsolin in dendritic spine[J].Biol Chem,2019,400(9):1129~1139. [10] Sun W,Yang J,Hong Y,et al.Lanthanum chloride impairs learning and memory and induces dendritic spine abnormality by down-regulating Rac1/PAK signaling pathway in hippocampus of offspring rats[J].Cell Mol Neurobiol,2020,40(3):459~475. [11] Zhao D,Meng J,Zhao Y,et al.RPS23RG1 is required for synaptic integrity and rescues alzheimer's disease-associated cognitive deficits[J].Biol Psychiatry,2019,86(3):171~184.