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1.
Genet Mol Res ; 16(1)2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28128418

RESUMO

To investigate the role of the P2X7 receptor in learning and memory dysfunction induced by HIV-1 envelope glycoprotein gp120 (gp120), we established HIV-1-associated dementia (HAD) animal models by intracerebroventricular (ICV) infusion of gp120 in rats. We observed gp120-induced cognitive dysfunction in the radial arm water maze test. Results showed that rats in the gp120 groups had longer escape latencies and more errors compared to those in the control group. For example, the average trial time in the 50-ng/day-gp120 group on day eight (16.57 ± 1.71 s, N = 90) was significantly longer than that of control rats (9.93 ± 0.68 s, N = 90). The relative expression of P2X7 mRNA in the control, 50-, 70-, and 100-ng/day-gp120 groups were 0.43 ± 0.06, 0.48 ± 0.07, 0.83 ± 0.05, and 0.84 ± 0.10, respectively; relative P2X7 protein expression in those groups was 0.63 ± 0.07, 1.08 ± 0.06, 0.90 ± 0.07, and 1.03 ± 0.11, respectively. According to immunohistochemistry analysis, the staining intensity values for P2X7 protein expression in the control, 50-, 70-, and 100-ng/d-gp120 groups were 0.88 ± 0.07, 1.41 ± 0.12, 1.28 ± 0.13, and 1.31 ± 0.10, respectively. The above results showed that the expression of P2X7 increased significantly in the hippocampus of gp120 rats compared to that of the control group. These results suggest that ICV infusion of gp120 can successfully mimic HAD in rats, and P2X7 may be involved in gp120-induced cognitive dysfunction. This could provide a theoretical foundation and potential drug target for research and treatment of ADC.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Hipocampo/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animais , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Expressão Gênica , Hipocampo/fisiopatologia , Humanos , Imuno-Histoquímica , Aprendizagem em Labirinto , Ratos , Receptores Purinérgicos P2X7/genética
2.
Genet Mol Res ; 15(2)2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27323041

RESUMO

This study was aimed at exploring the effects of P2X7 receptors on gp120-induced injury and naringin's protective effects against gp120-induced injury in BV2 microglia. BV2 microglia injury model was established by gp120 treatment and MTS assay was used to verify whether naringin has a cell-protective effect against gp120-induced injury. Changes in P2X7 receptor expression were assayed using RT-PCR, qPCR, and western blot. Results showed that the ODs of the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.91 ± 0.10, 0.71 ± 0.09, 0.83 ± 0.10, and 0.83 ± 0.10, respectively. Compared to the control group, the gp120 group showed a significantly decreased cell survival rate. Cell survival rates of the gp120+naringin group increased significantly compared to those of the gp120 group, while no difference was observed when compared to the gp120+BBG group. The relative P2X7 mRNA expression levels in the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.73 ± 0.06, 1.05 ± 0.06, 0.78 ± 0.05, and 0.81 ± 0.04, respectively. The corresponding P2X7 protein expression levels were 0.46 ± 0.04, 0.79 ± 0.04, 0.38 ± 0.07, and 0.42 ± 0.06. P2X7 mRNA and protein expression in the gp120 group increased significantly compared to those in the control group, and declined in the gp120+naringin group compared to those in the gp120 group. Therefore, P2X7 receptors might be involved in gp120-induced injury in BV2 microglia, and naringin might play a protective role by inhibiting the up-regulated expression of P2X7 receptors.


Assuntos
Flavanonas/farmacologia , Proteína gp120 do Envelope de HIV/toxicidade , Microglia/efeitos dos fármacos , Receptores Purinérgicos P2X7/metabolismo , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/metabolismo , Complexo AIDS Demência/virologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Microglia/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Purinérgicos P2X7/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
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