RESUMO
Alzheimer's disease (AD) is the most common dementia and the trigger of its pathological cascade is widely believed to be the overproduction and accumulation of ß-amyloid protein (Aß) in the affected brain. However, effective AD remedies are still anxiously awaited. Recent evidence suggests that curcumin may be a potential agent for AD treatment. In this study, we used 5×FAD transgenic mice as an AD model to investigate the effects of curcumin on AD. Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aß production by downregulating BACE1 expression, preventing synaptic degradation, and improving spatial learning and memory impairment of 5×FAD mice. These findings suggest that curcumin is a potential candidate for AD treatment.
Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/biossíntese , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/biossíntese , Curcumina/uso terapêutico , Transtornos da Memória/metabolismo , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácido Aspártico Endopeptidases/genética , Curcumina/farmacologia , Expressão Gênica , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
OBJECTIVE: This study aimed to observe the effect of local mild hypothermia on regional cerebral blood flow (rCBF) after acute intracerebral hemorrhage (ICH) and to evaluate its relation to clinical outcome in patients with ICH. METHODS: 36 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were randomly assigned to 2 group: local mild hypothermia with conventional mannitol (Group A) or conventional mannitol (Group B). SPECT study was performed at day 7 after therapy. The SPECT images were semi-quantitatively analyzed, and the radioactivity ratios of lesion to normal tissue (L/NT) were calculated. National Institutes of Health Stroke Scale (NIHSS) were used in evaluation at days 14 and 21 after therapy. RESULTS: There were significant differences in NIHSS score at days 14 and 21, and the L/NT ratios between the groups A and B (P < 0.05). Based on GCS, more patients in the group A showed favorable outcomes than patients in the group B (P < 0.05). Furthermore, the L/NT ratios significantly increased in patients with favorable outcomes compared to poor outcomes. Changes in NIHSS score at days 14 and 21 were closely negatively correlated with the L/NT ratios in the groups A and B (r= -0.58, -0.61, and -0.52, -0.75, respectively, P < 0.05). CONCLUSION: Local mild hypothermia could significantly increase rCBF and improve clinical outcome in ICH patients as evaluated by
Assuntos
Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/terapia , Circulação Cerebrovascular , Cisteína/análogos & derivados , Hipertermia Induzida/métodos , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Doença Aguda , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.