Effects Of Dihydrotestosterone On Hippocampal Spatial Learning Memory And Synaptic Plasticity In SAMP8 Male Mice Under Continuous Hypoxia

Objective: The behavior of SAMP8 male mice treated with DHT u nder continuous hypoxic conditions was observed in the Morris water m aze experiment and space exploration experiment.To investigate the effe ct of DHT on spatial learning and memory in mice.To observe the ex pression of HIF-1α,SYN,PSD-95 and Drebrin in hippocampus of SAM P8 male mice under continuous hypoxia.To investigate the changes of hippocampal morphology,HIF-1α and the expression of synaptic plasticit y related proteins SYN,PSD-95 and Drebrin in castrated mice treated with DHT,and to understand the effect of androgen on synaptic plastici ty in hippocampal mice.Methods: Experiments are grouped into Control group(Control),H ypoxia group(Hypoxia),Dihydrotestosterone group(DHT),Dihydrotestos terone+Hypoxic group(DHT+Hypoxia),using water maze(Morris water maze,MWM)experiment,testing each male castration spatial learning and memory ability in mice.In the first 2 days,the mice adapted to le arning and were trained 4 times a day for 3-7 days.The escape latency was recorded in the location-based navigation experiment in mice.On t he 8th day,the space exploration experiment was carried out,and the ti mes of mice crossing the platform area in 120 seconds and the time of staying in the quadrant where the platform is located were recorded.Golgi-Cox staining assay was used to detect the changes in the density of synaptic dendritic spines in hippocampal CA1 region.The expression of Hif-1α,Cited2,Epo,Epor,Creb,Glut1,Erk,Syn,Psd-95 and Drebrin genes were detected by RT-PCR.The protein expressions of ERK,P-ERK,GLUT1,SYN,PSD-95 and Drebrin were detected by Western blot.Results: 1.Data analysis showed that the incubation period of the four groups of castrated animals was shortened to different degrees within 5 days of the localization cruise experiment.There was no significant difference in incubation period between the Control group and the Hypoxia group.The escape latency of DHT group was significantly shorter than that of Control group.With the extension of days,the incubation period was further shortened,and the difference was statistically significant(P<0.05).The incubation period of the Hypoxia + DHT group was shorter than that of the Hypoxia group on day 5,and the difference was statistically significant(P<0.05).The space exploration and cross-platform experiment showed that the swimming track of mice in the Control group and the Hypoxia group was mostly aimlessly circled around the edge of the pool.The trajectory of Hypoxia + DHT group was obviously disordered.The movement trajectory of the DHT group was mainly concentrated near the target quadrant.Statistical analysis of the target quadrant time of each group showed that the target quadrant time of the DHT group was significantly longer than that of the Control group,and the differences were statistically significant(P<0.05).The target quadrant time of the Hypoxia +DHT group was slightly longer than that of the Control group,but the difference was not statistically significant.2.The density of synaptic dendritic spines in DHT group and DHT+Hypoxia group was significantly higher than that in Control group by Golgi-Cox staining.The density of the Hypoxia group was lower than that of the Control group,and there was no significant difference.3.The expression changes of Hif-1α,Cited2,Epo,Epor,Erk,Glut1,Syn,Psd-95 and Drebrin genes were detected by RT-PCR.Statistical analysis showed that Hif-1α expression was increased in the Hypoxia group and the DHT group compared with the Control group,and the expression of Epo and Epor were increased in the Hypoxia group,and the expression of Hypoxia+DHT group was also increased.The expression of Erk,Glut1,Syn,Psd-95 and Drebrin gene increased in DHT group,DHT +Hypoxia group was slightly higher than Control group,but the difference was not statistically significant.4.The protein expressions of ERK,p ERK,GLUT1,PSD95,Drebrin,SYN and IBA1 were detected by Western blot.Statistical analysis showed that the protein expressions of ERK,p ERK,GLUT1 and PSD95 were increased in the DHT group and the Hypoxia +DHT group compared with the Control group,while the protein expressions of Drebrin and Syn were significantly increased in the Hypoxia +DHT group compared with the Control group,but there was no significant difference in the increase in the Hypoxia +DHT group.There was statistically significant difference in the expression of IBA1 protein between the Hypoxia group and the Hypoxia +DHT group.Conclusions:1.DHT can improve the spatial learning and memory ability of male SAMP8 castrated mice.DHT had a certain tendency to improve the spatial learning and memory ability of male SAMP8 castration mice under continuous hypoxia condition,but there was no statistical significance.2.DHT promotes the expression of synaptic plasticity proteins PSD95,Drebrin and SYN in hippocampal neurons through HIF-1α,ERK and GLUT1 signaling pathways.3.Under the condition of persistent hypoxia,the increased expression of IBA1 protein indicates the activation of microglial cells in brain tissue.