Anxiety and the aging brain: stressed out over p53?
Anxiety and the aging brain: stressed out over p53?
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焦虑和大脑老化：p53 压力过大？
DOI：
10.1016/j.bbagen.2009.09.007
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Medrano,Silvia
中科院分区：
文献类型：
--
作者：
Scrable,Heidi;Burns-Cusato,Melissa;Medrano,Silvia
我们提出了一个模型，在这个模型中，衰老大脑中的细胞丢失被视为损害老年人生活质量的行为变化的根本原因，包括广泛性焦虑症的发病。根据这一模型，当成人大脑神经源性区域的干细胞失去再生能力时，磨损、死亡或受损的神经元无法被替换，从而留下功能缺口。由于大多数替换都直接或间接地涉及抑制性中间神经元，最终结果是随着时间的推移获得了一种超兴奋状态。应激轴受到成人大脑中所有三个神经源性区域的辅助，使其特别容易受到这些与年龄相关的变化的影响。我们概述了应力轴的过度兴奋进而激活肿瘤抑制基因P53的分子机制。这加强了干细胞增殖能力的丧失，并干扰了糖皮质激素受体关闭神经内分泌通路和重置轴的反馈机制。
We propose a model in which cell loss in the aging brain is seen as a root cause of behavioral changes that compromise quality of life, including the onset of generalized anxiety disorder, in elderly individuals. According to this model, as stem cells in neurogenic regions of the adult brain lose regenerative capacity, worn-out, dead, or damaged neurons fail to be replaced, leaving gaps in function. As most replacement involves inhibitory interneurons, either directly or indirectly, the net result is the acquisition over time of a hyper-excitable state. The stress axis is subserved by all three neurogenic regions in the adult brain, making it particularly susceptible to these age-dependent changes. We outline a molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53. This reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanism by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.