Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CBMSO), Spanish Research Council (CSIC)-Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain.
Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
J Neurosci. 2021 Mar 24;41(12):2541-2553. doi: 10.1523/JNEUROSCI.0675-20.2020.
The rodent hippocampus generates new neurons throughout life. This process, named adult hippocampal neurogenesis (AHN), is a striking form of neural plasticity that occurs in the brains of numerous mammalian species. Direct evidence of adult neurogenesis in humans has remained elusive, although the occurrence of this phenomenon in the human dentate gyrus has been demonstrated in seminal studies and recent research that have applied distinct approaches to birthdate newly generated neurons and to validate markers of adult-born neurons. Our data point to the persistence of AHN until the 10th decade of human life, as well as to marked impairments in this process in patients with Alzheimer's disease. Moreover, our work demonstrates that the methods used to process and analyze postmortem human brain samples can limit the detection of various markers of AHN to the point of making them undetectable. In this Dual Perspectives article, we highlight the critical methodological aspects that should be strictly controlled in human studies and the robust evidence that supports the occurrence of AHN in humans. We also put forward reasons that may account for current discrepancies on this topic. Finally, the unresolved questions and future challenges awaiting the field are highlighted.
啮齿动物的海马体在其一生中会产生新的神经元。这一过程被称为成年海马神经发生(adult hippocampal neurogenesis,AHN),是一种在许多哺乳动物大脑中发生的显著的神经可塑性形式。尽管已有开创性的研究和最近的研究应用了不同的方法来标记新生成的神经元并验证成年神经元的标记物,证明了人类齿状回中存在成年神经发生,但仍未能直接证明人类存在成年神经发生。我们的数据表明,AHN 一直持续到人类生命的第 10 个十年,并且在阿尔茨海默病患者中,这一过程明显受损。此外,我们的工作表明,用于处理和分析人脑尸检样本的方法可能会限制对 AHN 各种标记物的检测,使其无法检测到。在这篇双视角文章中,我们强调了在人类研究中应严格控制的关键方法学方面,以及支持人类发生 AHN 的有力证据。我们还提出了可能导致目前在该主题上存在差异的原因。最后,突出了该领域有待解决的问题和未来的挑战。