I studied adult neurogenesis in mice and it for sure is real. Weather the new findings by Frisen in Striatum will be verified with other methods remains to be seen and strongly depends on the development of new techniques. But even in humans there is old data from cancer patients treated with BrdU that proves adult neurogenesis. Here you could argue, well they had cancer that might boost proliferation throughout the body, but since it is backuped by so many animal studies and Frisens carbon method I say it is real. "adult neurogenesis" has 1803 hits today on pubmed. number increasing.

It is always good to remain very critical and be careful what to translate from animals to human, but in general do not underestimate the force of plasticity in adult, including synaptogenesis, neurogenesis and volumetric/functional changes measured by fMRI. We are highly , flexible adults in general, this does not just come from the activation of existing pathways.

adult neurogeneisis was first described by Josef Atlman in the 1960s. It was only re-discovered in the 1980s.

I studied adult neurogenesis in mice and it for sure is real. Weather the new findings by Frisen in Striatum will be verified with other methods remains to be seen and strongly depends on the development of new techniques. But even in humans there is old data from cancer patients treated with BrdU that proves adult neurogenesis. Here you could argue, well they had cancer that might boost proliferation throughout the body, but since it is backuped by so many animal studies and Frisens carbon method I say it is real. "adult neurogenesis" has 1803 hits today on pubmed. number increasing.

It is always good to remain very critical and be careful what to translate from animals to human, but in general do not underestimate the force of plasticity in adult, including synaptogenesis, neurogenesis and volumetric/functional changes measured by fMRI. We are highly , flexible adults in general, this does not just come from the activation of existing pathways.

Jonathan,

have a look to this paper.

http://www.mdpi.com/1422-0067/15/1/1554

Something related to issues above.

I believe that much of adult neurogenesis is NOT adult neurogenesis.

I'd suggest Dr. Jose Luis Trejo's work at http://www.cajal.csic.es/ingles/departamentos/trejo-perez/trejo-perez.html.

@Adalberto, this publication assumes that H3 phosphorylation is always neccesary for proliferation. Epigenetics is a very new field in biology with very few known "facts". H3 phosphorylation is related to proliferation, but if it is a neccesary precondition has not been shown!!! Epigenetics are quite different depending on the cell type you are looking at. Just to name a few examples where it is known to be highly variable: H3K9 methylation (sometimes activates, sometimes inhibits), microRNAs (are believed in general to repress gene expression, but sometimes elevate it), etc....

Adult Neurogenesis on the other hand has been shown with different methods since 1945...

In addition to that, the dynamics of BrdU staining in the adult mammalian brain correlate with the expansion, migration and integration of pools of labeled newborn neurons which are born and selected in the neurogenic niche examined (OB or DG, for example). What inferred through BrdU (or IDU/CDU) labeling has been of course validated in-vitro in several studies. I do believe there is no doubt that in the adult mammalian brain neurogenesis goes on. I think what Johnatan meant was being skeptical about human adult striatal neurogenesis. Which indeed is an important result that probably needs further confirmation, given its novelty.

I agree that the evidence seems strong for the hypothesis of adult neurogenesis especially in the dentate gyrus but also in the olfactory bulb. I think the strongest data comes from retroviral labeling with a reporter gene (eg. GFP). Retroviral labeling facilitates morphological and electrophysiological characterization following newborn neural progenitors as they differentiate into neurons.

The main point of this question concerns whether the methods used by Ernst et al., are specific for proliferation as opposed to DNA repair. Has anyone seen evidence from retroviral labeling to confirm that new neurons are formed in the adult striatum?

It will probably be important to consider species specific differences because Ernst et al., point out that the RMS produces neurons in the OB of rodents but not humans. Bedard et al., 2006 reported BrdU labeling of neurons in the striatum of the adult squirrel monkey. However, these cells expressed DARP-32 in contrast to the IdU labeled neurons in the human striatum that were all negative for DARP-32.

Article Chemical characterization of newly generated neurons in the ...

The same group put out a paper showing adult neurogenesis in the adult hippocampus. In cell too

http://www.cell.com/retrieve/pii/S0092867413005333

Adult neurogenesis is real, these C14 studies are pretty much irrefutable.

But it occurs at levels so low the utility is next to nothing. For degenerative disorders, cell replacement is the only viable option for replacing the lost cells.

You could manipulate the adult neurogenesis regions to increase their rate, but the manipulation would be so extreme it is so remote that this would ever work or be clinically acceptable.

olfactory neurons are born throughout our life. Neurogenesis exists in humans and being restricted solely to olfaction is unlikely. But thanks for raising this critical thoughts! Highly appreciated.

The question whether thymidine analog incorporation in adult newborn neurons reflects DNA repair rather than DNA replication has been asked from the very beginning of studying adult neurogenesis.

In fact, the nucleotide incorporation after DNA repair is pretty negligible compared to DNA synthesis (where the genome is doubled). Therefore, people have checked that BrdU is readily detectable in cycling cells and their immediate progeny, but not in cells undergoing DNA repair (see attached Paper Figures 1A-C). Following these lines, I would assume that it is pretty challenging to detect EdU or DNA that was incorporated after the A-bomb tests by C14 methods after DNA repair.

Christian

I think it may be important to consider the duration of exposure to the label. It seems that DNA repair could lead to accumulating label over time during a long term exposure. C14 from the nuclear bomb or IdU for cancer treatment would be relatively long term compared to most of the BrdU labeling experiments that have been used to compare proliferation to DNA repair.

Are there any experiments that compared proliferation to DNA repair with long term labeling in vivo?

Jonathan

I am at least not aware of such experiments. The challenge would be to have a system where one can exclude the contribution of e. g. adult neurogenesis and cell fusion to the labeling. However, as a matter of fact, treatments that strongly induce DNA-repair such as cranial radiation (used in cancer treatment) strongly reduce BrdU incorporation in the adult neurogenic niches in vivo (see attached paper). Moreover, if the C14 and IdU labeling in the Ernst et al. paper as well as the other C14 papers from Frisén lab should result from long-term DNA-repair in neurons, why would that repair be restricted to the hippocampus and the striatum, but not be detectable in the olfactory bulb, the cortex and the overall brain? At least there seems to be some specificity...

New evidence . . .

NEUROGENESIS

A striatal supply of new neurons

Leonie Welberg

Nature Reviews Neuroscience 15, 203 (2014)

Neurogenesis: A striatal supply of new neurons http://go.nature.com/j2DGQc

Thanks Alfonso,

The abstract is here;

http://www.cell.com/retrieve/pii/S0092867414001378

.

I can't access the full text article.

Paul.

Dear Johnathan,

I think that more important than knowing if neurogenesis is real or not based on methods to detect it, is the physiological role of new neurons either on striatum or hippocampus, olfactory bulbs, or other cerebral areas should be investigated.

Since there was so much controversy regarding neurogenesis from Altman's paper on the 60's until the paper you cited we still discuss the existence of this phenomena.

I think we should move on to investigate its physiological relevance.

Best regards

Paul

The full pape here.

Alfonso

I think that the work of René Hen and Alex Dranovsky is very compelling in relation to hippocampal neurogenesis and human depression and SSRI treatment. See their 2006 review and then more recent papers

I think this paper have a nice discussion about pitfalls, limitations and validation of using DNA techniques for approving neurogenesis:

http://www.sciencedirect.com/science/article/pii/S0165017306001044

Good point, Mike. The use of multiple approaches is essential for a conclusive argument. Skepticism is healthy in may cases, however. Our own work on sheep brain tells us very clearly that we are getting cell division in the hippocampus (easily detected pairs of cells marked with BrDU within 2 hours of treatment with pheromones), but is it neurogenesis (new neurons as opposed to other cell types)? Open mind required. It is exciting, however!

I studied adult neurogenesis or cell proliferation in different strains of wild caught rodents and it is very evident especially in the two established region, subventricular zone (SVZ) and dentate gyrus (DG) of the hippocampus. Other region with neurogenic potential includes, striatum, cortex, amygdala etc. So it is no longer debate. However, rate of adult cell proliferation versus cell death is what is now being investigated. Maybe as new cells are being added it correlates to cell death.

It seems this discussion gained a new chapter, at least in humans. Sorrells er al., 2018 have found the generation of new neurons drops to undetectable levels in adulthood. But, few weeeks later, Boldrini et al., 2018, showed adult neurogenesis persist even in older humans, without reduction with aging. it is a big controversy that perhaps can reside in some methodological differences. There are good reviews considering some aspects related to these different finds, but lacks a deep discussion regarding how does human brain ( DG and Hp) deal with such a huge amount of information in absence of newly neurons ( the biggest plastic event in the brain)?