Protective effect of CD73 inhibitor α, ß-methylene ADP against amyloid-ß-induced cognitive impairment by inhibiting adenosine production in hippocampus

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.

Avaliaçäo da auto hemostasia, em pacientes com Síndrome de Down, por meio de provas de coagulaçäo, contagem de plaquetas e agregaçäo plaquetária estimulada por agonistas / Evaluation of Down's patients hemostasis by coagulation tests, platelet count and platelet binding stimulated by agonists

Objetivando avaliar a hemostasia em pacientes com Síndrome de Down, a autora apresenta nesta tese uma casuíatica de 21 pacientes, os quais foram submetidos aos seguintes exames pré-operatórios: TTPA, TP, TT, contagem de plaquetas e agregaçäo plaquetária estimulada por agonistas (Adrenalina, ADP, AA, Colágeno, PAF e 5HT). Os resultados apresentaram-se dentro dos limites da normalidade para as provas de coagulaçäo e contagem de plaquetas. Encontramos tendência hipoagregante frente a estimulaçäo por adrenalina, ADP, AA, colágeno e PAF, e näo observamos diferenças significantes para a agregaçäo plaquetária estimulada pelo 5HT, quando comparada com o grupo controle normal