PTK2B affects the levels of Aβ in blood and brain and behavioral functions via targeting LRP-1 transporter in Aβ-induced cognitive dysfunction mice / 生理学报

The aim of the present study was to explore the correlation between ptk2b/PTK2B (protein tyrosine kinase 2 beta, a ptk2b-encoded protein) and the level of low density lipoprotein receptor-related protein-1 (LRP-1), as well as to uncover the relationship between the changes in beta amyloid protein (Aβ) levels in blood and brain and the expression of ptk2b in Aβ-induced cognitive dysfunction mice. A total of 64 3-month-old C57BL/6J mice were divided randomly into the experimental group and control group. All mice underwent the intracerebroventricular (i.c.v.) intubation. Mice in the experimental group received the i.c.v. infusion of oligomeric Aβ

Dexmedetomidine-mediated Wnt Pathway Inhibits Sevoflurane-induced Cognitive Impairment in Neonatal Rats / 中国医学科学院学报

Objective To explore the effect of dexmedetomidine(Dex)on sevoflurane-induced cognitive impairment in neonatal rats through Wnt signaling pathway. Methods Sixty 7-day-old SD rats were assigned into five groups:control group(without any intervention),Dex group(intraperitoneal injection of 25 μg/kg Dex),sevoflurane group(3% sevoflurane treatment for 4 hours),sevoflurane+Dex group(inhalation of 3% sevoflurane after injection of 25 μg/kg Dex for 4 hours),and sevoflurane+Dex+Wnt inhibitor group(Wnt inhibitor XAV393 and 25 μg/kg Dex were injected and 3% sevoflurane was inhaled for 4 hours).Three weeks later,Morris water maze was used to detect the cognitive function;TdT-mediated dUTP nick end labeling(TUNEL)staining was performed to detect the apoptosis of hippocampal neurons;neuronal nuclei (NeuN) staining was conducted to detect the survival of hippocampal neurons;Western blot was carried out to detect the expression of apoptosis-related proteins.The expression of the factors involved in Wnt/GSK-3β/β-catenin signaling pathway was detected by fluorescence quantitative polymerase chain reaction,and Western blot. Results Compared with the control group,there was no significant difference in the escape latency of Dex group(t=0.304,P=0.768);the escape latency in sevoflurane group(t=5.823,P=0.002),sevoflurane+Dex group(t=3.188,P=0.010),and sevoflurane+Dex+Wnt inhibitor group(t=5.784,P=0.002)was significantly prolonged.Compared with that in the sevoflurane group,the escape latency in sevoflurane+Dex group(t=3.646,P=0.005)was significantly shortened.Compared with that in sevoflurane+Dex group,the escape latency in sevoflurane+Dex+Wnt inhibitor group(t=3.296,P=0.008)was prolonged.Compared with that in the control group,the times of crossing platform in sevoflurane group(t=5.179, P=0.004),sevoflurane+Dex group(t=2.309,P=0.043),and sevoflurane+Dex+Wnt inhibitor group(t=3.871, P=0.003)decreased.Compared with that in sevoflurane group,the times of crossing platform in sevoflurane+Dex group(t=3.296,P=0.008)significantly increased.Compared with that in sevoflurane+Dex group,the times of crossing platform in sevoflurane+Dex+Wnt inhibitor group(t=2.361, P=0.041)reduced.Compared with the control group,there was no significant difference in the number of apoptotic cells in Dex group(t=1.920,P=0.127),and the number of apoptotic cells in sevoflurane group,sevoflurane+Dex group,and sevoflurane+Dex+Wnt inhibitor group increased by 16%(t=13.436,P=0.002),5%(t=7.752, P=0.001),and 11.5%(t=12.612,P=0.002),respectively.Compared with that in the sevoflurane group,the number of apoptotic cells in sevoflurane+Dex group and sevoflurane+Dex+Wnt inhibitor group decreased by 11%(t=8.521,P=0.002)and 5.5%(t=3.123,P=0.036),respectively.Compared with that in the sevoflurane+Dex group,the number of apoptotic cells in sevoflurane+Dex+Wnt inhibitor group increased by 6.5%(t=6.250,P=0.003).Compared with that in the control group,the number of positive cells in 0.15 mm

Use of psychoactive drugs predicts functional disability among older adults / Uso de psicofármacos prediz incapacidade funcional entre idosos

ABSTRACT OBJECTIVE: Investigate whether the use of psychoactive drugs would be a predictor of incidence of functional disability among seniors living in community. METHODS: It is a population-based longitudinal study, developed between January 1, 1997 and December 31, 2011, with older adults living in community. The association between the use of psychoactive drugs and the development of functional disability for instrumental (IADLs) and basic (BADLs) activities of daily living was tested using the extended Cox proportional hazards model, which considers the measure of exposure of interest throughout the follow-up period. The analyses were stratified by sex and adjusted by sociodemographic characteristics, health behavior and health conditions. RESULTS: After multivariate adjustment, the use of two or more psychoactive drugs in the female stratum was associated with disability for both IADLs (HR = 1.58; 95%CI 1.17-2.13) and BADLs (HR = 1.43; 95%CI 1.05-1.94), the use of benzodiazepines was associated with disability for IADLs (HR = 1.32; 95%CI 1.07-1.62), and the use of antidepressants was associated with disability for both IADLs (HR = 1.51; 95%CI 1.16-1.98) and BADLs (HR = 1.44; 95%CI 1.10-1.90). In the male stratum, the use of antipsychotics was associated with disability for IADLs (HR = 3.14; 95%CI 1.49-6.59). CONCLUSIONS: The study showed a prospective association between the use of psychoactive drugs and functional disability. These results indicate the need to carefully assess the prescription of psychoactive drugs for older adults and monitor their usage in order to detect damages to the health of users.

RESUMO OBJETIVO: Investigar se o uso de psicofármacos seria um preditor da incidência de incapacidade funcional entre idosos residentes em comunidade. MÉTODOS: Trata-se de um estudo longitudinal de base populacional, desenvolvido entre primeiro de janeiro de 1997 e 31 de dezembro de 2011, junto a idosos residentes em comunidade. A associação entre o uso de psicofármacos e o desenvolvimento de incapacidade funcional para atividades instrumentais (AIVD) e básicas (ABVD) de vida diária foi testada por meio do modelo de riscos proporcionais de Cox estendido, que considera a medida da exposição de interesse ao longo de todo o tempo de seguimento. As análises foram estratificadas por sexo e ajustadas por características sociodemográficas, comportamento em saúde e condições de saúde. RESULTADOS: Após ajuste multivariado, no estrato feminino o uso de dois ou mais psicofármacos foi associado à incapacidade tanto para AIVD (HR = 1,58; IC95% 1,17-2,13) quanto para ABVD (HR = 1,43; IC95% 1,05-1,94), o uso de benzodiazepínicos se manteve associado à incapacidade para AIVD (HR = 1,32; IC95% 1,07-1,62) e o uso de antidepressivos se manteve associado à incapacidade, tanto para AIVD (HR = 1,51; IC95% 1,16-1,98) quanto para ABVD (HR = 1,44; IC95% 1,10-1,90). No estrato masculino, o uso de antipsicóticos foi associado à incapacidade para AIVD (HR = 3,14; IC95% 1,49-6,59). CONCLUSÕES: O estudo evidenciou uma associação prospectiva entre o uso de psicofármacos e a incapacidade funcional. Esses resultados indicam a necessidade de avaliar cuidadosamente a prescrição de psicofármacos para idosos e monitorar o seu uso, buscando detectar prejuízos à saúde dos seus usuários.