河北医科大学学报 ›› 2023, Vol. 44 ›› Issue (7): 754-759,791.doi: 10.3969/j.issn.1007-3205.2023.07.003

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双氢睾酮对持续低氧SAMP8雄性小鼠空间学习记忆及突触可塑性的影响

  

  1. 1.河北医科大学基础医学院人体解剖学教研室，河北 石家庄 050017；2.河北省石家庄市第三医院呼吸科，河北 石家庄 050011；3.河北医科大学第二医院呼吸二科，河北 石家庄 050000

  • 出版日期:2023-07-25 发布日期:2023-07-24
  • 作者简介:韩硕（1974-），男，河北石家庄人，河北医科大学基础医学院讲师，医学博士，从事神经退行性疾病基础研究。
  • 基金资助:
    河北省自然科学基金（H2019206316）

Effects of dihydrotestosterone on spatial learning memory and synaptic plasticity in SAMP8 male mice under continuous hypoxia

  1. 1.Department of Human Anatomy, the School of Basic Medicine, Hebei Medical University, Shijiazhuang 
    050017, China; 2.Department of Respiratory Medicine, the Third Hospital of Shijiazhuang City, 
    Hebei Province, Shijiazhuang 050011， China; 3.the Second Department of Respiratory Medicine, 
    the Second Hospital of Hebei Medical University, Shijiazhuang 050000，China
  • Online:2023-07-25 Published:2023-07-24

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摘要： 目的 探讨持续低氧条件下SAMP8雄性小鼠，在给予双氢睾酮(dihydrotestosterone,DHT)后海马空间学习记忆及突触可塑性的影响。了解雄激素对快速衰老小鼠海马突触可塑性的影响。
方法 健康成年5月龄雄性SAMP8小鼠40只，随机分为Control组、DHT组、Hypoxia组和DHT+Hypoxia组，每组8只。应用Morris水迷宫实验，检测小鼠的空间学习记忆能力。Golgi-cox染色实验检测海马CA1区突触树突棘密度变化。RT-PCR和Western blot检测相关基因和蛋白的表达。
结果 Hypoxia组逃避潜伏期明显长于Control组，DHT组逃避潜伏期明显短于Control组和Hypoxia组（P＜0.05）。DHT组目标象限时间明显延长于Control组，跨越平台次数明显大于Control组（P＜0.05）。DHT组和DHT+Hypoxia组海马CA1区突触树突棘密度明显高于Control组和Hypoxia组（P＜0.05）。Hypoxia组Hif-1α、Epo、Epor表达高于Control组，Glut1、Syn、Psd-95、Drebrin表达低于Control组，DHT组Hif-1α、Erk、Glut1、Syn 、Psd-95、Drebrin基因表达高于Control组，DHT+Hypoxia组Hif-1α、Epo表达高于Control组（P＜0.05）;DHT组Hif-1α、Epo低于Hypoxia组，Erk、Glut1、Syn、Psd-95、Drebrin表达高于Hypoxia组，DHT+Hypoxia组Hif-1α低于Hypoxia组，Glut1、Syn、Psd-95、Drebrin表达高于Hypoxia组（P＜0.05）。Hypoxia组ERK、pERK、Glut1、PSD95蛋白表达低于Control组，Iba1蛋白表达高于Control组，DHT组ERK、pERK、Glut1、PSD95、Drebrin、SYN、Iba1蛋白表达高于Control组，DHT+Hypoxia组ERK、pERK、Glut1、PSD95、Iba1蛋白表达高于Control组（P＜0.05）;DHT组ERK、pERK、Glut1、PSD95、Drebrin、SYN蛋白表达高于Hypoxia组,Iba1蛋白表达低于Hypoxia组,DHT+Hypoxia组ERK、pERK、Glut1、PSD95蛋白表达高于Hypoxia组（P＜0.05）。
结论 双氢睾酮可通过Hif-1α、ERK、Glut1信号通路促进海马神经元的突触可塑性，改善了空间学习记忆能力。


关键词: 认知功能障碍, 双氢睾酮, 空间学习, 低氧

Abstract:

Objective To investigate the effects of dihydrotestosterone (DHT) on spatial learning and memory and synaptic plasticity in hippocampus of SAMP8 male mice under continuous hypoxia, and to understand the effect of androgen on hippocampal synaptic plasticity in rapidly aging mice. 

Methods Forty healthy adult (5-month-old) male SAMP8 mice were randomly divided into Control group, DHT group, Hypoxia group, and DHT+Hypoxia group, with 8 mice in each group. Morris water maze was used to detect the spatial learning and memory abilities of mice. Golgi-cox staining was used to detect the density changes of synaptic dendritic spine in hippocampal CA1. RT-PCR and Western blot were used to detect the expression of related genes and proteins. 
Results The escape latency of the Hypoxia group was significantly longer than that of the Control group, while the escape latency of the DHT group was significantly shorter than that of the Control group and the Hypoxia group (P＜0.05). The target quadrant time in the DHT group was significantly longer than that in the Control group, and the number of crossing platform was significantly greater than that in the Control group (P＜0.05). The density of synaptic dendritic spine in hippocampal CA1 region in the DHT group and the DHT+Hypoxia group was significantly higher than that in Control group and the Hypoxia group (P＜0.05). Hif-1α, Epo and Epor expression of Hypoxia group was higher than that of the Control group, while the expression of Glut1, Syn, Psd-95, and Drebrin was lower than that of the Control group. The expression of Hif-1α, Erk, Glut1, Syn, Psd-95, and Drebrin genes in the DHT group was higher than that of the Control group, while the expression of Hif-1α and Epo gene of  the DHT+Hypoxia group was higher than that of the Control group (P＜0.05). Hif-1α and Epo expression in DHT group was lower than that in Hypoxia group, and Erk, Glut1, Syn, Psd-95, and Drebrin expression was higher than that in Hypoxia group; Hif-1α was lower in the DHT+Hypoxia group than that in the Hypoxia group, and Glut1, Syn, Psd-95, and Drebrin expression was higher than that in the Hypoxia group (P＜0.05). The protein expression of ERK, pERK, Glut1, and PSD95 was lower in the Hypoxia group than in the Control group, while Iba1 was higher than that in the Control group. The protein expression of ERK, pERK, Glut1, PSD95, Drebrin, SYN, and Iba1 in the DHT group was higher than that in the Control group, and the protein expression of ERK, pERK, Glut1, PSD95, and Iba1 in the DHT+Hypoxia group was higher than in the Control group (P＜0.05). The expression of ERK, pERK, Glut1, PSD95, Drebrin, and SYN proteins in the DHT group was higher than that in the Hypoxia group, while the expression of Iba1 protein was lower than that in the Hypoxia group. The expression of ERK, pERK, Glut1, and PSD95 proteins in the DHT+Hypoxia group was higher than that in the Hypoxia group (P＜0.05). 
Conclusion Dihydrotestosterone can promote the synaptic plasticity of hippocampal neurons and improve the spatial learning and memory abilities via  HIF-1α, ERK and GLUT1 signaling pathways. 



Key words: cognitive dysfunction, dihydrotestosterone, spatial learning, hypoxia

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