Effects of Dex on alleviating cognitive impairment induced by myocardial I/R in aged mice and its related synaptic plasticity mechanisms
10.3969/j.issn.1009-0126.2024.10.021
- VernacularTitle:右美托咪定减轻老年小鼠心肌缺血再灌注诱发认知功能障碍的作用及突触可塑性机制
- Author:
Hui ZHAO
1
;
Xiaoqian WEI
;
Danqiong WANG
;
Yuan CHEN
Author Information
1. 030032 太原,山西白求恩医院综合医疗科
- Keywords:
dexmedetomidine;
myocardial reperfusion injury;
cognitive dysfunction;
synapses
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(10):1215-1220
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and synaptic plasticity mechanism of dexmedetomi-dine(Dex)on alleviating cognitive impairment induced by myocardial ischemia/reperfusion(I/R)in aged mice.Methods Forty elderly male C57BL/6 mice were randomly divided into sham group,Sham+Dex group,I/R group,and I/R+Dex group,with 10 mice in each group.On the 7th day of reperfusion,cognitive function was evaluated using an eight arm water maze and novel ob-ject recognition.Electrophysiological recordings of hippocampal CA1 area was performed to meas-ure field excitatory postsynaptic potential(fEPSP)in in vivo long-term potentiation(LTP).The serum levels of cardiac troponin T(cTnT),lactate dehydrogenase(LDH),and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were detected by ELISA.Western blotting was used to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)-FL,and TrkB-T1 in hippocampal tissues.Golgi-Cox staining was utilized to observe the density of dendritic spines in hippocampal CA1 area.Immunofluorescence staining was performed to detect the expression of synaptic growth factor(SYN)and postsynaptic dense protein 95(PSD95).Results On the 7th day of reperfusion,the working memory error(WME),reference memory errors(RME)and total errors(TE)of the eight arm water maze and the expression lev-els of cTnT,LDH,NT-proBNP and TrkB-T1 were significantly higher,and the recognition index,fEPSP and expression levels of BDNF,TrkB-FL,SYN and PSD95 and density of dendritic spines were remarkably decreased in the I/R group and I/R+Dex group than the Sham group and Sham+Dex group(P＜0.05).The I/R+Dex group had obviously reduced TrkB-T1 expression(0.86±0.07 vs 1.51±0.18),and increased expression levels of BDNF(0.70±0.07 vs 0.39±0.06),TrkB-FL(0.67±0.10 vs 0.45±0.08),SYN(20.53±0.59 vs 16.50±1.05)and PSD95(17.73±0.52 vs 14.71±0.91)when compared with the I/R group(P＜0.05).Conclusion Dex exerts protective effect on cognitive impairment induced by myocardial I/R in elderly mice,and the specific mecha-nism may be related to alleviating cardiac injury,increasing the expression of BDNF,SYN and PSD95,improving the imbalance of TrkB-FL and TrkB-T1 ratio in hippocampal tissue,and enhan-cing synaptic plasticity.
