Abrous Djoher Nora, Koehl Muriel, Le Moal Michel
Laboratoire de Physiopathologie des Comportements, Institut National de la Sané et de la Recherche Médicale, U588, Université de Bordeaux, France.
Physiol Rev. 2005 Apr;85(2):523-69. doi: 10.1152/physrev.00055.2003.
The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.
成年哺乳动物大脑可从干细胞样细胞群中产生新神经元这一发现，是神经科学领域的一项突破。有趣的是，这种特殊的大脑结构可塑性新形式似乎特定于离散的脑区，并且大多数研究集中于海马结构（HF）的脑室下区（SVZ）和齿状回（DG）。总体而言，在过去二十年中出现了两条主要研究路线：第一条旨在了解神经干细胞样细胞（及其后代）的基本生物学特性以及新生神经元融入现有神经网络的情况，而第二条则侧重于了解其在脑功能中的相关性，这在DG中得到了更广泛的研究。在此，我们概述了关于成体神经发生及其对成体大脑功能相关性的当前知识。我们首先分析阻碍该领域进展的方法学问题，并描述主要的神经发生位点及其特异性。我们将看到，尽管取得了相当大的进展，但新生神经元在宿主神经回路中的解剖学和功能整合水平仍有待阐明。然后简要介绍控制神经元命运的细胞内机制以及调节成体神经发生的外在因素。我们将看到，已经确定了越来越多的表观遗传因素，它们根据所考虑的神经发生位点表现出作用特异性。最后，我们回顾了在生理条件下将神经发生与海马功能以及海马相关病理（如癫痫、情绪障碍和成瘾）发展联系起来所取得的进展。这是促进治疗策略发展的必要步骤。
