JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (7): 11-15.doi: 10.6040/j.issn.1671-7554.0.2014.010

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Effect of donepezil on hypothalamic-pituitary-adrenocortical-axis in Alzheimer’s disease rats

WANG Jinhong1, LI Wentao2, YU Shutian1, DONG Li1   

  1. 1. Department of Pharmacology, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Functional Laboratory, Weifang Medical University, Weifang 261053, Shandong, China
  • Received:2014-01-06 Revised:2014-06-10 Online:2014-07-10 Published:2014-07-10

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Abstract: Objective To investigate the effect of donepezil on hypothalamic-pituitary-adrenocortical-axis(HPA)in Alzheimer's disease (AD) rats. Methods A total of 30 healthy male Wistar rats were injected into amyloid β-protein 25-35 (Aβ25-35) intracerebroventricularly and D-galactose (D-gal) intraperitoneally to prepare AD model and divided into normal control group, AD model group, and donepezil group randomly, and 10 rats in each group. Serum hydrocortisone (HYD) and adrenocorticotropic hormone (ACTH) concentrations were detected by radioimmunoassay. Morphology of hypothalamus was observed with transmission electron microscope, and the expressions of corticotropin releasing hormone (CRH) and CRH receptor 1 (CRHR1) were observed by immunohistochemical method. Results Compared with normal control group, learning ability of model rats decreased (P<0.05), HYD concentration increased (P<0.01), ACTH concentration decreased significantly (P<0.01), and the expressions of CRH and CRHR1 reduced. The ultrastructure of hypothalamus of model rats were damaged. Compared with AD model group, donepezil decreased serum concentration of HYD and increased serum concentration of ACTH in the AD rats (P<0.05 or P<0.01 respectively), and improved the expressions of CRH and CRHR1, which protected ultrastructure damage of hypothalamus. Conclusion Donepezil improves the function of HPA in AD rats and shows treatment effect on AD.

Key words: Donepezil, Adrenocorticotropic hormone, Alzheimer’s disease rats, Corticotropin releasing hormone, Hydrocortisone

CLC Number: 

  • R574
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