Effect of activating α7 nicotinic acetylcholine receptor on learning and memory function and microglia in traumatic brain injury model rat
10.3760/cma.j.cn371468-20230702-00305
- VernacularTitle:激活α7烟碱型乙酰胆碱受体对创伤性脑损伤模型大鼠学习记忆功能及小胶质细胞的影响
- Author:
Juan DU
1
;
Han ZHANG
;
Yuxuan YANG
;
Bo ZHANG
Author Information
1. 川北医学院第二临床医学院南充市中心医院康复医学科，南充 637000
- Keywords:
Traumatic brain injury;
α7 nicotinic acetylcholine receptor;
Microglia;
Cognitive dysfunction;
Rat
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2024;33(2):116-121
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of activating α7 nicotinic acetylcholine receptor(α7nAChR)on cognitive function and polarization of hippocampal microglia in traumatic brain injury (TBI) rats.Methods:Totally 36 male SD rats with 6-8 weeks old were randomly divided into Sham group ( n=12), TBI group ( n=12), TBI+ α7nAChR agonist group ( n=6) and TBI+ α7nAChR antagonist group( n=6). The TBI model was established by the " free fall impact" method. From the 4th to 6th day after modeling, mice in the TBI+ α7nAChR agonist group were intraperitoneally injected with α7nAChR agonist PNU-282987 (3 mg/kg). Rats in TBI+ α7nAChR antagonist group were intraperitoneally injected with α7nAChR antagonist methyllycaconitine citrate (5 mg/kg) first, then 45 minutes later they were injected with α7nAChR agonist PNU-282987 (3 mg/kg). Rats in the TBI group and Sham group were intraperitoneally injected with an equal volume of 0.9% sodium chloride solution. Morris water maze test was used to evaluate the learning and memory function of rats. Immunofluorescence staining was used to observe the ionized calcium binding adapter molecule 1 (Iba-1)(a marker for microglia) and arginase 1 (Arg-1)(a marker for M2 microglia). Western blot was used to detect the protein level of Arg-1 in hippocampal tissue. Statistical analysis was performed using GraphPad Prism 9 software. Independent sample t test was used for comparison between two groups, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for multiple comparison. Results:The results of the water maze test showed that after 7 days of modeling, there was a statistical difference in the escape latency among the 4 groups of rats ( F=6.134, P<0.05). There was no statistical difference in the escape latency between the TBI group and the TBI+ α7nAChR antagonist group( P>0.05), but the both were higher than that of the Sham group (both P<0.05). The escape latency of the TBI+ α7nAChR agonist group((31.87±9.01)s) was shorter than that of the TBI group((56.75±2.62)s) and the TBI+ α7nAChR antagonist group((60.00±0.00)s) (both P<0.05). The results of immunofluorescence staining showed that there were statistical differences in the fluorescence intensity and cell numbers of Arg-1 + /Iba-1 + among the four groups ( F=17.37, 9.33, both P<0.05). The immune fluorescence intensity (0.27±0.03) and cell numbers (21.67±4.41) of Arg-1 + /Iba-1 + in the TBI+ α7nAChR agonist group were higher than those in the TBI group((0.14±0.03), (11.33±2.60)) and TBI+ α7nAChR antagonist group((0.10±0.03), (7.67±1.20)) (all P<0.05). The results of Western blot showed that there was a statistical difference in the level of Arg-1 protein in hippocampus among the 4 groups ( F=8.323, P=0.001). There was no significant difference in the level of Arg-1 protein between the TBI group and the TBI+ α7nAChR antagonist group( P>0.05), and the level of Arg-1 protein in the TBI+ α7nAChR agonist group(1.06±0.22) was higher than that in the TBI group(0.60±0.13) and TBI+ α7nAChR antagonist group(0.35±0.10) (both P<0.05). Conclusion:Activating α7nAChR can promote the polarization of M2 type microglia in rat hippocampal tissue and improve the learning and memory function of TBI rats.
