Protective effect of CD73 inhibitor α, ß-methylene ADP against amyloid-ß-induced cognitive impairment by inhibiting adenosine production in hippocampus
Electron. j. biotechnol
; Electron. j. biotechnol;48: 53-61, nov. 2020. ilus, graf
Article
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| LILACS
| ID: biblio-1254710
Biblioteca responsável:
CL1.1
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms.RESULTS:
We found that acute administration of Aß142 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß142-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect.CONCLUSIONS:
In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß142 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Difosfato de Adenosina
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Doenças Neurodegenerativas
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Hipocampo
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Nucleotidases
Limite:
Animals
Idioma:
En
Revista:
Electron. j. biotechnol
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Chile