Weeks Janis C
Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403-1254, USA.
Prog Neurobiol. 2003 Aug;70(5):421-42. doi: 10.1016/s0301-0082(03)00102-3.
Steroid hormones act via evolutionarily conserved nuclear receptors to regulate neuronal phenotype during development, maturity and disease. Steroid hormones exert 'global' effects in organisms to produce coordinated physiological responses whereas, at the 'local' level, individual neurons can respond to a steroidal signal in highly specific ways. This review focuses on two phenomena-the loss of dendritic processes and the programmed cell death (PCD) of neurons-that can be regulated by steroid hormones (e.g. during sexual differentiation in vertebrates). In insects such as the moth, Manduca sexta, and fruit fly, Drosophila melanogaster, ecdysteroids orchestrate a reorganization of neural circuits during metamorphosis. In Manduca, accessory planta retractor (APR) motoneurons undergo dendritic loss at the end of larval life in response to a rise in 20-hydroxyecdysone (20E). Dendritic regression is associated with a decrease in the strength of monosynaptic inputs, a decrease in the number of contacts from pre-synaptic neurons, and the loss of a behavior mediated by these synapses. The APRs in different abdominal segments undergo segment-specific PCD at pupation and adult emergence that is triggered directly and cell-autonomously by a genomic action of 20E, as demonstrated in cell culture. The post-emergence death of APRs provides a model for steroid-mediated neuroprotection. APR death occurs by autophagy, not apoptosis, and involves caspase activation and the aggregation and ultracondensation of mitochondria. Manduca genes involved in segmental identity, 20E signaling and PCD are being sought by suppressive subtractive hybridization (SSH) and cDNA microarrays. Experiments utilizing Drosophila as a complementary system have been initiated. These insect model systems contribute toward understanding the causes and functional consequences of dendritic loss and neurodegeneration in human neurological disorders.
类固醇激素通过进化上保守的核受体发挥作用，在发育、成熟和疾病过程中调节神经元表型。类固醇激素在生物体中发挥“全局”作用以产生协调的生理反应，而在“局部”水平上，单个神经元可以以高度特异性的方式对类固醇信号作出反应。本综述聚焦于两种现象——树突状突起的丧失和神经元的程序性细胞死亡（PCD），这两种现象可受类固醇激素调节（如在脊椎动物的性别分化过程中）。在诸如烟草天蛾和果蝇等昆虫中，蜕皮类固醇在变态过程中协调神经回路的重组。在烟草天蛾中，幼虫末期辅助植物牵缩肌（APR）运动神经元会因20-羟基蜕皮酮（20E）水平升高而发生树突丧失。树突退化与单突触输入强度降低、突触前神经元接触数量减少以及这些突触介导的行为丧失有关。不同腹部节段的APR在化蛹和成虫羽化时会经历节段特异性PCD，如细胞培养所示，这是由20E的基因组作用直接且细胞自主触发的。APR羽化后的死亡为类固醇介导的神经保护提供了一个模型。APR死亡是通过自噬而非凋亡发生的，涉及半胱天冬酶激活以及线粒体的聚集和超浓缩。正在通过抑制性消减杂交（SSH）和cDNA微阵列寻找参与节段身份、20E信号传导和PCD的烟草天蛾基因。已启动利用果蝇作为互补系统的实验。这些昆虫模型系统有助于理解人类神经系统疾病中树突丧失和神经退行性变的原因及功能后果。
