MSGID: 1:317/3 642ba7eb
PID: hpt/lnx 1.9.0-cur 2019-01-08
TID: hpt/lnx 1.9.0-cur 2019-01-08
 How do we know if our brain is capable of repairing itself? 

  Date:
      April 3, 2023
  Source:
      Netherlands Institute for Neuroscience - KNAW
  Summary:
      Is our brain able to regenerate? And can we harness this
      regenerative potential during aging or in neurodegenerative
      conditions? These questions sparked intense controversy within
      the field of neuroscience for many years. A new study shows why
      there are conflicting results and proposes a roadmap on how to
      solve these issues.


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FULL STORY
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Is our brain able to regenerate? And can we harness this regenerative
potential during aging or in neurodegenerative conditions? These questions
sparked intense controversy within the field of neuroscience for many
years. A new study from the Netherlands Institute for Neuroscience shows
why there are conflicting results and proposes a roadmap on how to solve
these issues.


==========================================================================
The notion of exploiting the regenerative potential of the human brain
in aging or neurological diseases represents a particularly attractive
alternative to conventional strategies for enhancing or restoring brain
function, especially given the current lack of effective therapeutic
strategies in neurodegenerative disorders like Alzheimer's disease. The
question of whether the human brain does possess the ability to
regenerate or not has been at the center of a fierce scientific debate
for many years and recent studies yielded conflicting results. A new
study from Giorgia Tosoni and Dilara Ayyildiz, under the supervision of
Evgenia Salta in the laboratory of Neurogenesis and Neurodegeneration,
critically discusses and re-analyzes previously published datasets. How
is it possible that we haven't yet found a clear answer to this mystery?
Previous studies in which dividing cells were labeled in postmortem human
brain, showed that new cells can indeed arise throughout adulthood in
the hippocampus of our brain, a structure that plays an important role
in learning and memory, and is also severely affected in Alzheimer's
disease. However, other studies contradict these results and cannot
detect the generation of new brain cells in this area. Both conceptual
and methodological confounders have likely contributed to these seemingly
opposing observations. Hence, elucidating the extent of regeneration in
the human brain remains a challenge.

New state-of-the-art technologies Recent advances in single-cell
transcriptomics technologies have provided valuable insights into
the different cell types found in human brains from deceased donors
with different brain diseases. To date, single-cell transcriptomic
technologies have been used to characterize rare cell populations
in the human brain. In addition to identifying specific cell types,
single-nucleus RNA sequencing can also explore specific gene expression
profiles to unravel full the complexity of the cells in the hippocampus.

The advent of single-cell transcriptomics technologies was initially
viewed as a panacea to resolving the controversy in the field. However,
recent single- cell RNA sequencing studies in human hippocampus yielded
conflicting results.

Two studies indeed identified neural stem cells, while a third study
failed to detect any neurogenic populations. Are these novel approaches --
once again - - failing to finally settle the controversy regarding the
existence of hippocampal regeneration in humans? Will we eventually be
able to overcome the conceptual and technical challenges and reconcile
these -seemingly- opposing views and findings?  Technical issues In this
study, the researchers critically discussed and re-analyzed previously
published single-cell transcriptomics datasets. They caution that
the design, analysis and interpretation of these studies in the adult
human hippocampus can be confounded by specific issues, which ask for
conceptual, methodological and computational adjustments. By re-analyzing
previously published datasets, a series of specific challenges were
probed that require particular attention and would greatly profit from
an open discussion in the field.

Giorgia Tosoni: 'We analyzed previously published single-cell
transcriptomic studies and performed a meta-analysis to assess whether
adult neurogenic populations can reliably be identified across different
species, especially when comparing mice and humans. The neurogenic
process in adult mice is very well characterized and the profiles of the
different cellular populations involved are known. These are actually
the same molecular and cellular signatures that have been widely used in
the field to also identify neurogenic cells in the human brain. However,
due to several evolutionary adaptations, we would expect the neurogenesis
between mice and humans to be different. We checked the markers for every
neurogenic cell type and looked at the amount of marker overlap between
the two species.'  'We found very little, if no, overlap between the two,
which suggests that the mouse-inferred markers we have been long using
may not be suitable for the human brain. We also discovered that such
studies require enough statistical power: if regeneration of neuronal
cells does happen in the adult human brain, we expect it to be quite
rare. Therefore, enough cells would need to be sequenced in order to
identify those scarce, presumably neurogenic populations.

Other parameters are also important, for example the quality of the
samples.

The interval between the death of the donor and the downstream
processing is critical, since the quality of the tissue and of the
resulting data drops over time.'  Reproducibility is key Dilara
Ayyildiz: 'These novel technologies, when appropriately applied,
offer a unique opportunity to map hippocampal regeneration in the
human brain and explore which cell types and states may be possibly
most amenable to therapeutic interventions in aging, neurodegenerative
and neuropsychiatric diseases. However, reproducibility and consistency
are key. While doing the analysis we realized that some seemingly small,
but otherwise very critical details and parameters in the experimental
and computational pipeline, can have a big impact on the results, and
hence affect the interpretation of the data.'  'Accurate reporting is
essential for making these single-cell transcriptomics experiments and
their analysis reproducible. Once we re-analyzed these previous studies
applying common computational pipelines and criteria, we realized that
the apparent controversy in the field may in reality be misleading:
with our work we propose that there may actually be more that we agree
on than previously believed.'
    * RELATED_TOPICS
          o Health_&_Medicine
                # Brain_Tumor # Nervous_System # Stem_Cells # Lymphoma
          o Mind_&_Brain
                # Brain-Computer_Interfaces # Brain_Injury # Neuroscience
                # Intelligence
    * RELATED_TERMS
          o Neuroscience o Neurobiology o Cognitive_neuroscience o
          Psychology o Psycholinguistics o Bioethics o Parkinson's_disease
          o Memory

==========================================================================
Story Source: Materials provided by
Netherlands_Institute_for_Neuroscience_-_KNAW. Note: Content may be
edited for style and length.


==========================================================================
Journal Reference:
   1. Giorgia Tosoni, Dilara Ayyildiz, Julien Bryois, Will Macnair,
   Carlos P.

      Fitzsimons, Paul J. Lucassen, Evgenia Salta. Mapping human
      adult hippocampal neurogenesis with single-cell transcriptomics:
      Reconciling controversy or fueling the debate? Neuron, 2023; DOI:
      10.1016/ j.neuron.2023.03.010
==========================================================================

Link to news story:
https://www.sciencedaily.com/releases/2023/04/230403133506.htm

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