RESUMEN
We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aß in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer's disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aß-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/terapia , Encéfalo/fisiopatología , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Fototerapia/métodos , Enfermedad de Alzheimer/psicología , Animales , Percepción Auditiva/fisiología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Miedo/fisiología , Expresión Génica , Proteínas de Andamiaje Homer , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Potenciación a Largo Plazo/fisiología , Masculino , Ratones Transgénicos , Neuronas/fisiología , Técnicas de Cultivo de Tejidos , Resultado del TratamientoRESUMEN
Six kinds of saponins (I, II, VII, PA, H) content of 22 samples of Paris polyphylla var. yunnanensis collected from different regions of Yunnan province were determined by HPLC, data was analyzed by SPSS 17. The results showed that the effect of altitude on saponin content was not significant, and the effect of growth area of saponins in P. polyphylla var. yunnanensis was significant, saponin content in sample from west Yunnan was significantly higher than that of samples from other regions.
Asunto(s)
Medicamentos Herbarios Chinos/análisis , Liliaceae/química , Saponinas/análisis , Altitud , China , Cromatografía Líquida de Alta PresiónRESUMEN
The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups. Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.