CRTD - Center for Regenerative Therapies Dresden, and DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany.
Eur J Neurosci. 2011 Mar;33(6):1018-24. doi: 10.1111/j.1460-9568.2011.07599.x.
Seven key elements describing the regulation of adult neurogenesis are proposed. (i) A distinction must be made between regulation and 'control' at the transcriptional level in order to appreciate the hierarchy of regulatory factors. (ii) The regulatory hierarchy comprises conceptual levels from behaviour to genes. Consequently, 'regulation' of neurogenesis can be confounded by confusing rather than integrating factors, levels and concepts. The immense spectrum of neurogenic regulators reflects the sensitivity of adult neurogenesis to many different types of stimuli, and provides a means of abstraction. (iii) Age per se does not seem to play a constant role in the modulation of this process, as the dramatic 'age-related' changes in adult neurogenesis only take place early in life. (iv) The regulatory hierarchy at any given time-point is corresponded by the directionality and sequential interdependence of different regulatory factors in the course of development. Regulation goes from non-specific to specific, and the following steps build on regulation at the previous ones. (v) This complexity is reflected at the genetic level in that adult neurogenesis is highly heritable and highly polygenic with single factors explaining little of the variance. (vi) As regulation is additive, there is an element of self-reinforcement in the regulation of adult neurogenesis, allowing the formation of regulatory reserves for situations of functional demand. (vii) The complexity of regulation makes adult neurogenesis sensitive to pathological disturbance at various levels, suggesting that different molecular events might result in similar and shared behavioural or functional phenotypes originating in the dentate gyrus.
提出了描述成人神经发生调节的七个关键要素。（i）为了理解调节因子的层次结构，必须在转录水平上区分调节和“控制”。（ii）调节层次结构包括从行为到基因的概念层次。因此，通过混淆而不是整合因素、层次和概念，“神经发生的调节”可能会混淆。神经发生调节因子的巨大谱反映了成年神经发生对许多不同类型刺激的敏感性，并提供了一种抽象的手段。（iii）年龄本身似乎并没有在调节这个过程中起到恒定的作用，因为成年神经发生的巨大“年龄相关”变化只发生在生命早期。（iv）在任何给定的时间点，调节层次结构都对应于不同调节因子在发育过程中的方向性和顺序相互依赖性。调节从非特异性到特异性，后续步骤建立在前一个步骤的调节之上。（v）这种复杂性在遗传水平上反映出来，即成年神经发生具有高度遗传性和高度多基因性，单个因素解释的变异很小。（vi）由于调节是累加的，因此在成年神经发生的调节中存在自我强化的因素，允许为功能需求的情况形成调节储备。（vii）调节的复杂性使成年神经发生对各种水平的病理干扰敏感，这表明不同的分子事件可能导致起源于齿状回的相似和共享的行为或功能表型。
