Analysis of proliferating neuronal progenitors and immature neurons in the human hippocampus surgically removed from control and epileptic patients

Seki, Tatsunori; Hori, Tomokatsu; Miyata, Hajime; Maehara, Michiyo; Namba, Tsuneo

doi:10.1038/s41598-019-54684-z

Cited by 45 publications

(39 citation statements)

References 68 publications

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“…For instance, a correlation between cognitive performance and neurogenic markers was observed in the monkey DG, as well as an age-related decline in proliferation/maturation markers (Ngwenya et al, 2015 ). Similarly, the presence of neuronal progenitors and immature neurons was recently reported in the human DG during physiological aging, and the number of these cells was found to be drastically affected by pathological conditions (Moreno-Jiménez et al, 2019 ; Seki et al, 2019 ).…”

Section: “Classical” Adult Neurogenic Zonessupporting

confidence: 52%

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Jurkowski

Bettio

Woo

et al. 2020

Front. Cell. Neurosci.

146

109

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Convincing evidence has repeatedly shown that new neurons are produced in the mammalian brain into adulthood. Adult neurogenesis has been best described in the hippocampus and the subventricular zone (SVZ), in which a series of distinct stages of neuronal development has been well characterized. However, more recently, new neurons have also been found in other brain regions of the adult mammalian brain, including the hypothalamus, striatum, substantia nigra, cortex, and amygdala. While some studies have suggested that these new neurons originate from endogenous stem cell pools located within these brain regions, others have shown the migration of neurons from the SVZ to these regions. Notably, it has been shown that the generation of new neurons in these brain regions is impacted by neurologic processes such as stroke/ischemia and neurodegenerative disorders. Furthermore, numerous factors such as neurotrophic support, pharmacologic interventions, environmental exposures, and stem cell therapy can modulate this endogenous process. While the presence and significance of adult neurogenesis in the human brain (and particularly outside of the classical neurogenic regions) is still an area of debate, this intrinsic neurogenic potential and its possible regulation through therapeutic measures present an exciting alternative for the treatment of several neurologic conditions. This review summarizes evidence in support of the classic and novel neurogenic zones present within the mammalian brain and discusses the functional significance of these new neurons as well as the factors that regulate their production. Finally, it also discusses the potential clinical applications of promoting neurogenesis outside of the classical neurogenic niches, particularly in the hypothalamus, cortex, striatum, substantia nigra, and amygdala.

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Section: “Classical” Adult Neurogenic Zonessupporting

confidence: 52%

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Jurkowski

Bettio

Woo

et al. 2020

Front. Cell. Neurosci.

146

109

View full text Add to dashboard Cite

show abstract

“…Even if most PSA-NCAM+ and DCX+ cells in the adult human hippocampus are not recently generated neurons, these neurons that have higher plasticity than mature neurons can be easily altered structurally and physiologically by an epileptic state. In fact, in both epileptic patients and epileptic model rodents, the abnormal structure of PSA-NCAM+ neurons are very similar to each other (Seki et al, 2019). Furthermore, some diseases, such as Alzheimer disease (Tobin et al, 2019) and epilepsy (Seki et al, 2019), are reported to show a decrease in the number of INM+ neurons, regardless of whether the INM+ cells are recently generated neurons or non-recently generated neurons.…”

Section: Application Of Rodent Studies To Understand Human "Postnatalmentioning

confidence: 93%

“…In this regard, a recent study using specimens surgically removed and immediately fixed, and subjected to antigen retrieval treatments clearly showed that a substantial number of PSA-NCAM+ neurons are distributed densely below the GCL, but the number of proliferating progenitors (Ki67+/HuB+/DCX+ cells) were very low (Seki et al, 2019). This suggests that immature-type neurons are not recently generated neurons, and the level of hippocampal neuronal production in adult humans is low.…”

Section: Recent Conflicting Reports In 2018 and 2019mentioning

confidence: 99%

“…Taken together, studies on AHN are entering a new era, in which knowledge of rodent studies are not simply applied to understand human AHN, but species differences in brain size, lifespan, and ways of life, and identity of INM-expressing cells must be considered to understand the true state and function of human AHN (Amrein et al, 2011;Faykoo-Martinez et al, 2017;La Rosa et al, 2019;Oppenheim, 2019;Seki et al, 2019;Snyder, 2019). Furthermore, comprehensive analyses of postnatally born neurons, both in infants and in adults, and INM-expressing neurons, regardless of their origin, will enable us to understand the state and function of human AHN and plasticity.…”

Section: Application Of Rodent Studies To Understand Human "Postnatalmentioning

confidence: 99%

“…In humans, DCX+ and PSA-NCAM+ cells have been identified in non-neurogenic regions of the neocortex ( Varea et al, 2007 ; Srikandarajah et al, 2009 ), amygdala ( Sorrells et al, 2019 ), and brain stem ( Yoshimi et al, 2005 ). Furthermore, PSA-NCAM+ cells have been found in the non-neurogenic regions of the hippocampal formation, such as the CA1/3, subiculum, and entorhinal cortex ( Mikkonen et al, 1998 , 1999 ; Seki et al, 2019 ).…”

Section: Validity Of Inms As Proxy Markers For Adult Neurogenesismentioning

confidence: 99%

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Understanding the Real State of Human Adult Hippocampal Neurogenesis From Studies of Rodents and Non-human Primates

Seki

2020

Front. Neurosci.

Self Cite

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The concept of adult hippocampal neurogenesis (AHN) has been widely accepted, and a large number of studies have been performed in rodents using modern experimental techniques, which have clarified the nature and developmental processes of adult neural stem/progenitor cells, the functions of AHN, such as memory and learning, and its association with neural diseases. However, a fundamental problem is that it remains unclear as to what extent AHN actually occurs in humans. The answer to this is indispensable when physiological and pathological functions of human AHN are deduced from studies of rodent AHN, but there are controversial data on the extent of human AHN. In this review, studies on AHN performed in rodents and humans will be briefly reviewed, followed by a discussion of the studies in non-human primates. Then, how data of rodent and non-human primate AHN should be applied for understanding human AHN will be discussed.

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Methods to study adult hippocampal neurogenesis in humans and across the phylogeny

et al. 2022

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The hippocampus hosts the continuous addition of new neurons throughout life—a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single‐cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long‐standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high‐quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.

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Analysis of proliferating neuronal progenitors and immature neurons in the human hippocampus surgically removed from control and epileptic patients

Cited by 45 publications

References 68 publications

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain

Understanding the Real State of Human Adult Hippocampal Neurogenesis From Studies of Rodents and Non-human Primates

Methods to study adult hippocampal neurogenesis in humans and across the phylogeny

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