Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (5): 1146-1153.doi: 10.13481/j.1671-587X.20210510

• Research in basic medicine • Previous Articles     Next Articles

Protective effect of limb ischemic training on neurons in hippocampal CA1 region of estrogen deprivation model rats and its mechanism

Jing XU1,2,Jiewei HU1,2,Lei TANG3,Chao XU2,4,Lu WANG2,4,Ming CHEN4,Wei YANG4,Ruimin WANG1,2,4()   

  1. 1.School Basic Medical Sciences,Hebei Key Laboratory for Chronic Diseases,North China University of Science and Technology,Tangshan 063210,China
    2.Tangshan Key Laboratory of Dementia and Dyscognitive,Hebei Province,Tangshan 063000,China
    3.Department of Pharmacy,School of Pharmacy,North China University of Science and Technology,Tangshan 063210,China
    4.Neurobiology Institute,School of Public Health,North China University of Science and Technology,Tangshan 063210,China
  • Received:2021-02-02 Online:2021-09-28 Published:2021-10-26
  • Contact: Ruimin WANG E-mail:ruimin-wang@163.com

Abstract: Objective

To investigate the protective effect of limb ischemia training (LIT) on the neurons in the hippocampal CA1 region of the estrogen-deprived rats, and to elucidate the possible molecular mechanism.

Methods

A total of 27 SD rats aged 3-4 months were undergone bilateral ovariectomy (OVX) to induce the estrogen deprivation models, and the model rats were randomly divided into OVX group (OVX), LIT group (OVX+LIT) and Letrozole(Let) group (OVX+LIT+ Let); there were 9 rats in each group. On the 7th day after OVX, LIT was performed in the rats once a day for 6 weeks;the rats in Let groups were given Let by intragastric administration at a dose of 10 mg·kg-1·d-1 for 6 weeks. Western bloting method was used to detect the expression levels of synaptic related protein (Synapsin1), myelin basic protein 2 (MBP2), postsynaptic dense protein(PSD95),cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB and brain-derived neurotrophic factor (BDNF)in the neurons of hippocampal CA1 region of the rats in various groups. Barns maze and novel object recognition test were used to detect the behavior indicators of the rats in various groups.

Results

Compared with OVX group, the expression levels of Synapsin1,PSD95,and MBP2 proteins in the neurons of hippocampal CA1 region of the rats in LIT group were significantly increased (P<0.05), and the expression levels of p-CREB and BDNF proteins were significantly increased(P<0.05). Compared with LIT group, the expression levels of Synapsin1, PSD95,and MBP2 proteins in the neurons of hippocampal CA1 region of the rats in Let group were significantly decreased (P<0.05), and the expression levels of p-CREB and BDNF proteins were also decreased(P<0.05). The results of Barnes maze test showed that compared with OVX group, the residence time in target quadrant of the rats in LIT group was prolonged, but there was no significant difference between two groups (P>0.05);compared with LIT group,the residence time in target quadrant in Let group was shortened(P<0.05).The results of Novel object recognition test showed that compared with OVX group, the time exploring the novel and old object of the rats in LIT group was prolonged,the discrimination index was increased,but there was no significant difference between two groups (P>0.05);compared with LIT group,the time exploring the novel object and old object of the rats in Let group was shortened, and the discrimination index was significantly decreased (P<0.05).

Conclusion

LIT can preserves the hippocampal CA1 neurons and cognitive function in the rats with estrogen deprivation by up-regulating CREB phosphorglation level and the protein levels of BDNF and synaptic proteins, and Let-treatment can inhibit the neuroprotective effect of LIT.

Key words: estrogen deprivation, limb ischemia training, letrozole, learning and memory

CLC Number: 

  • R45