Relationship between intracerebroventricular GDNF-induced improvement in long-term postoperative cognitive function and expression of PKMζ and Kalirin in hippocampus of neonatal rats
10.3760/cma.j.cn131073.20230929.00407
- VernacularTitle:脑室内注射GDNF改善新生大鼠术后远期认知功能与海马PKMζ和Kalirin表达的关系
- Author:
Yi CHEN
1
;
Zhen JIA
;
Yuxin ZHENG
;
Yize LI
;
Yonghao YU
;
Guolin WANG
Author Information
1. 天津医科大学总医院麻醉科 天津市麻醉学研究所，天津 300052
- Keywords:
Glial cell line-derived neurotrophic factor;
Postoperative cognitive complications;
Protein kinase C;
Kalirin
- From:
Chinese Journal of Anesthesiology
2024;44(4):418-423
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between intracerebroventricular glial cell line-derived neurotrophic factor (GDNF)-induced improvement in long-term postoperative cognitive function and expression of PKMζ and Kalirin in the hippocampus of neonatal rats.Methods:Sixty 7-day old Sprague-Dawley rats, male or female, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), GDNF group (group G), surgery group (group S) and surgery plus GDNF group (group S+ G). Group C did not receive anesthesia, surgery or drug treatment. Group G received intracerebroventricular injection of 0.3 μg recombinant rat GDNF. Group S and group S+ G underwent right carotid artery exposure surgery under 3% sevoflurane anesthesia, and in addition group S+ G received intracerebroventricular injection of GDNF. The Barnes maze test and the fear conditioning test were performed starting from postnatal day 33. The animals were then sacrificed under sevoflurane anesthesia after behavioral testing, the brains were obtained and divided into 2 halves sagittally along the midline. The left half of the brain was used for Golgi staining to observe dendritic morphology and measure dendritic spine density. The hippocampal protein was extracted from the right half of the brain to detect the expression of PKMζ and Kalirin by Western blot. Results:Compared with group C, the time to identify the target box in the Barnes maze test was significantly prolonged, the context-related freezing time in the fear conditioning test was shortened, the total dendritic length, the number of branches, the number of intersections in sholl analysis and spinal density in the hippocampus were reduced, and the expression of PKMζ and Kalirin was down-regulated in group S ( P<0.05), and no significant change was found in the aforementioned parameters in group G ( P>0.05). Compared with group S, the time to identify the target box in the Barnes maze test was significantly shortened, the context-related freezing time in the fear conditioning test was prolonged, the total dendritic length, the number of branches, the number of intersections in sholl analysis and spinal density in the hippocampus were increased, and the expression of PKMζ and Kalirin was up-regulated in group S+ G ( P<0.05). Conclusions:The mechanism by which intracerebroventricular GDNF improves long-term postoperative cognitive function may be related to up-regulating the expression of PKMζ and Kalirin and promoting the development of dendrites and dendritic spines in the hippocampus of neonatal rats.
