Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus
Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus
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DOI：
10.1523/jneurosci.0676-20.2020
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发表时间：
2021-03-24
影响因子：
5.3
通讯作者：
Alvarez-Buylla, Arturo
中科院分区：
文献类型：
--
作者：
Sorrells, Shawn F.;Paredes, Mercedes F.;Alvarez-Buylla, Arturo
成年海马神经发生最初是在啮齿动物身上发现的。随后的研究确定了成人神经干细胞，并发现成人神经发生与可塑性、行为和疾病之间存在重要联系。然而，在健康衰老过程中，人类齿状回(DG)是否会产生新的神经元仍然存在争议。我们和其他人很容易在婴儿的海马体中观察到表达双重皮质素(DCX)的未成熟细胞附近有增殖的神经前体细胞，但这种细胞的数量在儿童中减少，在成年人中几乎没有。最近利用双重抗原修复的研究发现，成人DG中有许多细胞被DCX抗体染色。这被解释为成人神经发生的高比率的证据，即使在较老的年龄也是如此。然而，这些DCX标记的细胞大多具有成熟的形态。此外，在成人DG中的研究还没有发现包含分裂祖细胞的生发区。在这篇双重视角的文章中，我们展示了在婴儿或成人的多个人脑区域中检测DCX不需要双重抗原恢复。我们回顾了以前的研究，并提供了新的数据表明DCX并不是新生神经元所独有的：DCX存在于成年杏仁核、内嗅觉神经元和海马旁皮质神经元中，尽管邻近的DG中没有DCX。对现有的RNA测序数据集的分析支持这样的观点，即DG神经发生在成年人的大脑中很少见或不存在。为了解决人类相互冲突的解释，有必要识别和可视化分裂的神经元前体，或者开发新的方法在单细胞水平上评估神经元的年龄。成年海马神经发生最初是在啮齿动物中发现的。随后的研究确定了成人神经干细胞，并发现成人神经发生与可塑性、行为和疾病之间存在重要联系。然而，在健康衰老过程中，人类齿状回(DG)是否会产生新的中性粒细胞仍存在争议。我们和其他人很容易在婴儿的海马体中观察到表达双重皮质素(DCX)的未成熟细胞附近有增殖的神经前体细胞，但这种细胞的数量在儿童中减少，在成年人中几乎没有。最近利用双重抗原修复的研究发现，成人DG中有许多细胞被DCX抗体染色。这被解释为成人神经发生的高比率的证据，即使在较老的年龄也是如此。然而，这些DCX标记的细胞大多具有成熟的形态。此外，在成人DG中的研究还没有发现包含分裂祖细胞的生发区。在这篇双重视角的文章中，我们展示了在婴儿或成人的多个人脑区域中检测DCX不需要双重抗原恢复。我们回顾了以前的研究，并提供了新的数据表明DCX并不是新生神经元所独有的：DCX存在于成年杏仁核、内嗅觉神经元和海马旁皮质神经元中，尽管邻近的DG中没有DCX。对现有的RNA测序数据集的分析支持这样的观点，即DG神经发生在成年人的大脑中很少见或不存在。为了解决人类这种相互矛盾的解释，有必要识别和可视化神经元前体的分裂，或者开发新的方法在单细胞水平上评估神经元的年龄。
Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interpreted as evidence for high rates of adult neurogenesis, even at older ages. However, most of these DCX-labeled cells have mature morphology. Furthermore, studies in the adult human DG have not found a germinal region containing dividing progenitor cells. In this Dual Perspectives article, we show that dual antigen retrieval is not required for the detection of DCX in multiple human brain regions of infants or adults. We review prior studies and present new data showing that DCX is not uniquely expressed by newly born neurons: DCX is present in adult amygdala, entorhinal and parahippocampal cortex neurons despite being absent in the neighboring DG. Analysis of available RNA-sequencing datasets supports the view that DG neurogenesis is rare or absent in the adult human brain. To resolve the conflicting interpretations in humans, it is necessary to identify and visualize dividing neuronal precursors or develop new methods to evaluate the age of a neuron at the single-cell level.Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neu-rons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe pro-liferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interpreted as evidence for high rates of adult neurogenesis, even at older ages. However, most of these DCX-labeled cells have mature morphology. Furthermore, studies in the adult human DG have not found a germinal region containing dividing progenitor cells. In this Dual Perspectives article, we show that dual antigen retrieval is not required for the detection of DCX in multiple human brain regions of infants or adults. We review prior studies and present new data showing that DCX is not uniquely expressed by newly born neurons: DCX is present in adult amygdala, entorhinal and parahippocampal cortex neurons despite being absent in the neighboring DG. Analysis of available RNA-sequencing datasets supports the view that DG neurogenesis is rare or absent in the adult human brain. To resolve the conflicting interpretations in humans, it is necessary to identify and visualize dividing neuronal precursors or develop new methods to evaluate the age of a neuron at the single-cell level.