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Aß promotes CD38 expression in senescent microglia in Alzheimer's disease
Hu, Yiran; Huang, Yan; Xing, Sanli; Chen, Chuan; Shen, Dingzhu; Chen, Jiulin.
  • Hu, Yiran; Shanghai University of Traditional Chinese Medicine. Shanghai. CN
  • Huang, Yan; Shanghai Geriatric Institute of Chinese Medicine. Shanghai. CN
  • Xing, Sanli; Shanghai Geriatric Institute of Chinese Medicine. Shanghai. CN
  • Chen, Chuan; Shanghai Geriatric Institute of Chinese Medicine. Shanghai. CN
  • Shen, Dingzhu; Shanghai Geriatric Institute of Chinese Medicine. Shanghai. CN
  • Chen, Jiulin; Shanghai Geriatric Institute of Chinese Medicine. Shanghai. CN
Biol. Res ; 55: 10-10, 2022. ilus
Article in English | LILACS | ID: biblio-1383914
ABSTRACT

BACKGROUND:

In Alzheimer's disease (AD), the neuroinflammatory response mediated by the activation of senescent microglia is closely related to energy dysmetabolism. However, the mechanism underlying the interaction between the energy metabolism of aging microglia and neuroinflammation remains unclear.

METHODS:

We used biochemical methods, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blot to determine the effects and mechanism of CD38 knockdown on energy metabolism and neuroinflammation in Aß1-40 injured BV2 cells. Using AD model mice, we detected CD38 enzyme activity, energy metabolism factors (ATP, NAD +, and NAD +/NADH), and neuroinflammatory factors (IL-1ß, IL-6, and TNF-α) following the addition of CD38 inhibitor. Using a combination of biochemical analysis and behavioral testing, we analyzed the effects of the CD38 inhibitor on energy metabolism disorder, the neuroinflammatory response, and the cognition of AD mice.

RESULTS:

Following Aß1-40 injury, SA-ß-Gal positive cells and senescence-related proteins P16 and P21 increased in BV2 cells, while energy-related molecules (ATP, NAD +, and NAD +/NADH) and mitochondrial function (mitochondrial ROS and MMP) decreased. Further studies showed that CD38 knockdown could improve Aß1-40-induced BV2 cells energy dysmetabolism and reduce the levels of IL-1ß, IL-6, and TNF-α. In vivo results showed an increase in senile plaque deposition and microglial activation in the hippocampus and cortex of 34-week-old APP/PS1 mice. Following treatment with the CD38 inhibitor, senile plaque deposition decreased, the number of Iba1 +BV2 cells increased, the energy metabolism disorder was improved, the proinflammatory cytokines were reduced, and the spatial learning ability was improved.

CONCLUSIONS:

Our results confirm that senescent microglia appeared in the brain of 34-week-old APP/PS1 mice, and that Aß1-40 can induce senescence of BV2 cells. The expression of CD38 increases in senescent BV2 cells, resulting in energy metabolism disorder. Therefore, reducing CD38 expression can effectively improve energy metabolism disorder and reduce proinflammatory cytokines. Following intervention with the CD38 inhibitor in APP/PS1 mice, the energy metabolism disorder was improved in the hippocampus and cortex, the level of proinflammatory cytokines was reduced, and cognitive impairment was improved.
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Full text: Available Index: LILACS (Americas) Main subject: Alzheimer Disease Type of study: Prognostic study Limits: Animals Language: English Journal: Biol. Res Journal subject: Biology Year: 2022 Type: Article Affiliation country: China Institution/Affiliation country: Shanghai Geriatric Institute of Chinese Medicine/CN / Shanghai University of Traditional Chinese Medicine/CN

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Full text: Available Index: LILACS (Americas) Main subject: Alzheimer Disease Type of study: Prognostic study Limits: Animals Language: English Journal: Biol. Res Journal subject: Biology Year: 2022 Type: Article Affiliation country: China Institution/Affiliation country: Shanghai Geriatric Institute of Chinese Medicine/CN / Shanghai University of Traditional Chinese Medicine/CN