New what! :- no neurogenesis
A re-examination of Sorrell et al and Boldrini et al
Adult Human Hippocampal Neurogenesis: Controversy and Evidence Hyunah Lee, Sandrine Thuret
At first, it may appear surprising that two studies use similar methods and reach completely opposite conclusions as to whether adult human hippocampal neurogenesis exists. However, a closer look at the subtle differences in their methods may provide clues to why this might have happened.
One of the key strengths of Boldrini and colleagues' study, not implemented by Sorrells and colleagues, is the use of stereology, which is widely regarded as the gold standard for unbiased quantification in histological studies. The adult brains examined by Sorrells and colleagues also had at least 20?h longer postmortem delay compared with those used by Boldrini and colleagues, which may have further diminished the immunoreactivity of markers such as DCX . Furthermore, the majority of control adults studied by Sorrells and colleagues had various diseases, such as cancer and stroke, whereas Boldrini and colleagues took rigorous measures to ensure that their subjects were physically and psychologically healthy. Therefore, it is difficult to say that the findings of Sorrells and colleagues represent adult human hippocampal neurogenesis in the general population, and there is a high chance that Boldrini and colleagues were more likely to have generated accurate estimates of neurogenesis in healthy human adults using a bias-free approach, such as stereology.
However, although Boldrini and colleagues used more reliable methods to study neurogenesis compared with Sorrells and colleagues, both studies share common ground in that they clearly demonstrate the limitations of studying this phenomenon in human postmortem brain tissue.
The markers that both research groups used are largely derived from characterization studies based on rodent models and, indeed, the majority of them have been shown to label postmortem human tissues in a similar pattern. However, species differences could make it difficult to generate 'reproducible' results when applying the same markers to study humans and, thus, raise the need to develop a different set of markers that can be readily used to detect the cell type of interest more reliably in humans. Notably, the absence of a proxy for in vivo human hippocampal neurogenesis may be the biggest obstacle hindering our progress in understanding the functional aspects of adult-born neurons in the hippocampus.
To actively address this issue, one could start by investigating the gene expression changes in the developing human brain at the transcriptomic level. For example, single-cell RNA-sequencing analysis on postmortem brain tissues that span a range of ages would help us to choose better molecular markers of human hippocampal neurogenesis. Advancements in non-invasive imaging and biomarker studies would also help us to investigate the role of adult-born neurons at the neural circuitry level and study the functional relevance of these neurons directly in human participants in the context of many interesting subjects that neurogenesis has been previously associated with, such as cognition, mental health, and lifestyle.
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