Effects of probiotics and docosahexaenoic acid on learning memory and brain damage in Aβ25-35-induced Alzheimer's disease mice
10.16438/j.0513-4870.2024-0634
- VernacularTitle:益生菌和二十二碳六烯酸对Aβ25-35诱导阿尔茨海默症小鼠学习记忆及脑损伤的作用
- Author:
Feng-xiao HAO
1
,
2
;
Meng-nan ZENG
1
,
2
;
Bing CAO
1
,
2
;
Xi-wen LIANG
1
;
Kai-li YE
1
,
2
;
Xin-mian JIAO
1
,
2
;
Wei-sheng FENG
1
,
2
;
Xiao-ke ZHENG
1
,
2
Author Information
1. College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou
2. The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou
- Publication Type:Research Article
- Keywords:
Alzheimer's disease;
probiotics;
ocosahexaenoic acid;
brain injury;
neuroinflammation
- From:
Acta Pharmaceutica Sinica
2024;59(11):3104-3116
- CountryChina
- Language:Chinese
-
Abstract:
The study aims to investigate and compare the effects of probiotics and docosahexaenoic acid (DHA) with the Alzheimer's disease (AD) therapeutic drug donepezil on the learning cognition and brain damage related indexes in AD mice, and to provide experimental basis for its treatment of AD. All animal experiments were approved by the Ethics Committee of the Henan University of Chinese Medicine (ethics number DWLL2018080003). Fifty male C57BL/6J mice were randomly assigned to one of five groups: sham-operated, model, donepezil (10 mg·kg-1), probiotic (2.7×109 CFU·d-1), and DHA (0.104 g·kg-1). Except for the sham-operated group, the AD animal model was established by injecting Aβ25-35 (200 μmol·L-1) in the lateral ventricle, followed by gavage administration for 4 weeks. In all mouse groups, learning memory ability, neuronal morphology in the hippocampus, apoptosis of primary hippocampal cells, and immune cell levels were detected. The levels of Aβ1-42, Aβ1-40, p-Tau, AchE, Ach, oxidative stress, glial cell activation, and the inflammatory factors IL-1β, IL-10, and TNF-α in the brain tissue of mice were also detected. 16S rDNA sequencing was used to further investigate the effects of donepezil and probiotics on AD. Donepezil, probiotics and DHA improved cognitive deficits and enhanced learning memory in Aβ25-35-induced mice by increasing locomotion time, locomotion distance, autonomic alternation rate, and shortening the time to reach the plateau; it significantly attenuated Aβ25-35-induced brain injury and neuroinflammation in mice by decreasing Aβ1-42, Aβ1-40, p-Tau, AchE, IL-1β, TNF-α, and MDA and increasing the levels of Ach, IL-10, GSH-Px, and T-SOD in brain tissues, as well as decreasing the activation of glial cells, and had a modulatory effect on immune cells. 16S rDNA sequencing shows that both donepezil and probiotics restore flora homeostasis and that differential bacteria are strongly associated with cognition, AD pathology, and neuroinflammation. Combining all indicators, donepezil and probiotics were more effective than DHA. All in all, donepezil, probiotics and DHA ameliorate Aβ25-35-induced cognitive dysfunction and brain damage in mice by modulating immune cells, reducing the number of apoptotic cells and glial cell activation in the brain, and decreasing the levels of oxidative stress and inflammatory factor expression, among which the effects of donepezil and probiotics were better than those of DHA, and the therapeutic effects of donepezil and probiotics on AD were closely related to the modulation of gut microbiome.
