RESUMEN
Since the world population is ageing, dementia is going to be a growing concern. Alzheimer's disease is the most common form of dementia. The pathogenesis of Alzheimer's disease is extensively studied, yet unknown remains. Therefore, we aimed to extract new knowledge from existing data. We analysed about 2700 upregulated genes and 2200 downregulated genes from three studies on the CA1 of the hippocampus of brains with Alzheimer's disease. We found that only the calcium signalling pathway enriched by 48 downregulated genes was consistent between all three studies. We predicted miR-129 to target nine out of 48 genes. Then, we validated miR-129 to regulate six out of nine genes in HEK cells. We noticed that four out of six genes play a role in synaptic plasticity. Finally, we confirmed the upregulation of miR-129 in the hippocampus of brains of rats with scopolamine-induced amnesia as a model of Alzheimer's disease. We suggest that future research should investigate the possible role of miR-129 in synaptic plasticity and Alzheimer's disease. This paper presents a novel framework to gain insight into potential biomarkers and targets for diagnosis and treatment of diseases.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Animales , Masculino , Análisis por Micromatrices , RatasRESUMEN
BACKGROUND/AIMS: Morphine causes state-dependent learning that its mechanism and brain-related structures are not fully understood. This study aimed to determine whether lidocaine reversible inactivation of the central nucleus of the amygdala (CeA) could affect acquisition, consolidation, and retrieval of morphine state-dependent learning. METHODS: One hundred twenty male Wistar rats were allocated into 15 experimental groups. Subcutaneous administration of morphine (5 mg/kg) induced morphine state-dependent learning. Intra-CeA injection of Lidocaine hydrochloride was performed 5 min before each morphine session for transient inactivation of the CeA. The step-through latency and the time spent in the dark compartment were measured using passive avoidance learning task. RESULTS: Our results showed that pretraining, posttraining, and pretest inhibition of the CeA severely impaired acquisition, consolidation, and retrieval of morphine state-dependent learning. CONCLUSION: These data revealed the involvement of the CeA in different stages of memory and morphine state-dependent learning.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Lidocaína/farmacología , Memoria/efectos de los fármacos , Morfina/farmacología , Analgésicos Opioides/farmacología , Anestésicos Locales/farmacología , Animales , Núcleo Amigdalino Central/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
The aim of the present study was to assess thealterations of corticolimbic microRNAs and protein expressions in the effect of scopolamine with or without stress on passive-avoidance memory in male Wistar rats. The expressions of miR-1, miR-10 and miR-26 and also the levels of p-CREB, CREB, C-FOS and BDNF in the prefrontal cortex (PFC), the hippocampus and the amygdala were evaluated using RT-qPCR and Western blotting techniques. The data showed that the administration of a muscarinic receptor antagonist, scopolamine or the exposure to 30â¯min stress significantly induced memory loss. Interestingly, the injection of an ineffective dose of scopolamine (0.5â¯mg/kg) alongside with exposure to an ineffective time of stress (10â¯min) impaired memory formation, suggesting a potentiative effect of stress on scopolamine response. Our results showed that memory formation was associated with the down-regulated expression of miR-1, miR-10 and miR-26 in the PFC and the hippocampus, but not the amygdala. The relative expression increase of miR-1 and miR-10 in the PFC and the hippocampus was shown in memory loss induced by scopolamine administration or 30-min stress. The PFC level of miR-10 and also hippocampal level of miR-1 and miR-10 were significantly up-regulated, while amygdala miR-1 and miR-26 were down-regulated in scopolamine-induced memory loss under stress. Memory formation increased BDNF, C-FOS and p-CREB/CREB in the PFC, the hippocampus and the amygdala. In contrast, the PFC, hippocampal and amygdala protein expressions were significantly decreased in memory loss induced by scopolamine administration (2â¯mg/kg), stress exposure (for 30â¯min) or scopolamine (0.5â¯mg/kg) plus stress (10â¯min). One of the most significant findings to emerge from this study is that the stress exposure potentiated the amnesic effect of scopolamine may via affecting the expressions of miRs and proteins in the PFC, the hippocampus and the amygdala. It is possible to hypothesis that corticolimbic signaling pathways play a critical role in relationship between stress and Alzheimer's disease.
Asunto(s)
Sistema Límbico/metabolismo , Trastornos de la Memoria/metabolismo , MicroARNs/metabolismo , Corteza Prefrontal/metabolismo , Estrés Psicológico/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Sistema Límbico/efectos de los fármacos , Masculino , Trastornos de la Memoria/inducido químicamente , Antagonistas Muscarínicos/metabolismo , Corteza Prefrontal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas Wistar , Escopolamina/administración & dosificación , Estrés Psicológico/inducido químicamenteRESUMEN
Morphine produces a state dependent learning. The hippocampus is involved in this kind of learning. Gap junctions (GJs) are involved in some of the effects of morphine and exist in different areas of the hippocampus. We investigated the effects of blocking GJ channels of the hippocampal CA1 area, by means of pre-test bilateral injection of carbenoxolone (CBX), on morphine state dependent learning, using a passive avoidance task. Post-training subcutaneous administrations of morphine (0.5, 2.5, 5 and 7.5 mg/kg) dose-dependently impaired memory retrieval. Pre-test administration of morphine (0.5, 2.5, 5 and 7.5 mg/kg) induced a state-dependent retrieval of the memory acquired under post-training morphine influence. Pre-test injections of CBX (25, 75 and 150 nM) dose dependently prevented memory retrieval by post-training (7.5 mg/kg) and pre-test (0.5, 2.5, 5, 7.5 mg/kg) injections of morphine. The results suggest that intercellular coupling via GJ channels of the hippocampal CA1 area modulates morphine state dependent learning.