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衰老与神经退行性疾病如帕金森综合征和阿尔茨海默征引起的神经易损性增高及中风和癫痫引起的神经元丧失相关联。一些研究揭示,细胞内钙离子浓度([Ca2+]i)升高引起神经元丧失与衰老相关疾病的发生有关。然而,以幼年和中年动物海马神经元为标本,直接进行[Ca2+]i和Ca2+稳态机制的比较研究尚未见报道。该研究应用Fura-2检测了幼年(4~5月)和中年(12~16月)SD大鼠快速分离的CA1区海马神经元[Ca2+]i。结果发现,中年大鼠神经元基础[Ca2+]i的水平明显高于幼年大鼠。用谷氨酸盐诱导胞内Ca2+超载,中年大鼠神经元转运多余Ca2+所需的时间比幼年大鼠长,这些研究结果为动物出现Ca2+稳态改变的年龄明显早于以往认为的老年阶段(≥24月)提供了直接的证据。Ca2+动力学的改变使衰老神经元对中风、癫痫或头部损伤相对于引起的神经元死亡更为敏感。阐明钙稳态机制不仅有助于理解衰老引起神经元丧失增多,而且也有助于开发靶向降低[Ca2+]i,进而维持衰老神经元正常钙稳态的临床药物。
Aging is associated with increased neurological vulnerability to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, and loss of neurons caused by stroke and epilepsy. Some studies have revealed that increased intracellular calcium concentration ([Ca2 +] i) causes neuronal loss associated with the development of aging-related diseases. However, comparative studies on the steady-state mechanism of [Ca2 +] i and Ca2 + have not yet been reported, taking the hippocampal neurons of young and middle-aged animals as specimens. In this study, Fura-2 was used to detect [Ca2 +] i in hippocampal CA1 hippocampus of SD rats isolated from young rats (4-5 months) and middle-aged (12-16 months) rats. The results showed that the level of basal [Ca2 +] i in neurons of middle-aged rats was significantly higher than that in young rats. Glutamate induced intracellular Ca2 + overload, middle-aged rat neurons required for the transport of excess Ca2 longer than juvenile rats, these findings are animals appear Ca2 + homeostasis was significantly earlier than previously thought in the elderly (≥ 24 months) provided direct evidence. Changes in Ca2 + kinetics make senile neurons more susceptible to stroke, epilepsy or head injury relative to the cause of neuronal death. To elucidate the mechanism of calcium homeostasis not only helps to understand that aging leads to increased neuronal loss, but also to the development of clinical drugs that target the reduction of [Ca2 +] i, thereby maintaining the normal calcium homeostasis in aged neurons.