[HN Gopher] Parkinson's gene may impair how new neurons are made...
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Parkinson's gene may impair how new neurons are made throughout our
lifetime
Author : gmays
Score : 68 points
Date : 2021-03-24 17:10 UTC (5 hours ago)
(HTM) web link (www.sheffield.ac.uk)
(TXT) w3m dump (www.sheffield.ac.uk)
| unfamiliar wrote:
| There's basically no more information in the article than in the
| headline.
| WWWWH wrote:
| There a link to the (open access) paper, so if you want the
| grizzly details they're all there for you.
| gwerbret wrote:
| "Parkinson's gene may impair how new neurons are made throughout
| our lifetime."
|
| This title is rather misleading, as the neurons relevant to
| Parkinson's disease are generally _not_ made at all, after birth.
| phcordner wrote:
| First line of the abstract of the paper:
|
| >Recent evidence suggests neurogenesis is on-going throughout
| life but the relevance of these findings for neurodegenerative
| disorders such as Parkinson's disease (PD) is poorly
| understood.
| aantix wrote:
| I've been taking magnesium l-threonate and l-theanine before
| bed, I seem to have more dreams and more intense dreams. I've
| seen both linked to neurogenesis.
|
| Is Mg deficiency part of the issue? https://www.ncbi.nlm.nih.
| gov/books/NBK507269/#_ch17_Low_Mg_a...
| ipaddr wrote:
| Mg threonine/ate usually is taken in the morning because it
| crosses the brain barrier causing an active response. I can
| see why you have active dreams. Try changing your mg type
| for less active nights.
| gwerbret wrote:
| They are misrepresenting the state of knowledge in that
| field. It has indeed been known -- since the 90s -- that
| there is ongoing neurogenesis in the human brain after birth.
| However, it is also well-known that these new neurons are
| produced in regions of the brain that are not relevant to
| Parkinson's. The specific neurons that are lost in this
| disease, from a region of the brain known as the substantia
| nigra, are not normally replaced by ongoing neurogenesis.
|
| (I say "not normally" because redirecting neurogenesis to
| supply new neurons to the substantia nigra, as a treatment
| for Parkinson's disease, has been an ongoing area of research
| for decades.)
|
| Note also that this research study was done with zebrafish,
| whose neurobiology is dramatically different from humans.
| phcordner wrote:
| This is also addressed in the paper:
|
| "Zebrafish are a particularly valuable tool to study
| neurogenesis in vertebrates. Basal levels of neurogenesis
| occur at higher levels than in mammals, and additional
| proliferative zones are found throughout the brain"
|
| In the zebrafish model, which yes, is different from the
| human brain, the researchers specifically demonstrate that
| neurogenesis is occurring in dopaminergic regions
| throughout life:
|
| "... we demonstrate that ascending TPp DA neurons and
| local-projecting PVO neurons, but not magnocellular
| ascending DA neurons, are each generated into adulthood in
| wild type animals at a rate that decreases with age."
|
| PINK1 deficiency slows the rate of the generation of DA
| neurons in zebrafish. Following this result, they then
| turned to the question of applicability to human systems by
| testing PINK1 deficiency on a culture of human midbrain
| organoids and successfully showed that this gene
| downregulated the size these organoids reached,
| demonstrating that this gene has an effect on neurogenesis
| of human dopaminergic neurons from the substantia nigra.
|
| "Isolated observations in animal models of PD always raise
| concerns about the applicability of any results to human
| patients with this condition. However, the observation of
| impairment of DA neurogenesis in a PINK1-deficient, human
| tissue derived organoid model confirmed the initial
| observations."
| gwerbret wrote:
| > demonstrating that this gene has an effect on
| neurogenesis of human dopaminergic neurons from the
| substantia nigra.
|
| But there is _no_ neurogenesis of human dopaminergic
| neurons in the adult substantia nigra.
|
| To create the organoid model, they used fibroblasts to
| generate induced pluripotent stem cells, and then
| differentiated these into neurons in culture. As an
| experimental model, this is fine, but it is not
| particularly indicative of actual human biology.
|
| The most you could probably infer from this paper is that
| IF there were dopaminergic progenitors in the human
| substantia nigra (there aren't), they MIGHT respond this
| way if you deleted PINK1.
| phcordner wrote:
| In neurobiology, human in vivo studies are prohibitive
| from a cost, logistical, and ethical standpoint. But to
| anyone who can successfully parse a neurobiology paper
| this is assumed knowledge.
| drewblaisdell wrote:
| > But there is no neurogenesis of human dopaminergic
| neurons in the adult substantia nigra.
|
| For my own understanding: how can we confidently assert
| that this is true?
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