5 ms·

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 brai

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 6y ago
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 6y ago
  > 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 6y ago
    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.
    - gwerbret 6y ago
      To return the goal posts to their original location, my premise was that the title "Parkinson's gene may impair how new neurons are made throughout our lifetime" is misleading, as the neurons in question are not actually made throughout our lifetimes. The referenced paper, which uses zebrafish and a somewhat contrived cell culture model, does not provide any new evidence about actual dopaminergic neurogenesis in humans. It is fair to say that if they'd actually demonstrated such neurogenesis actually occurs, with or without PINK1, the paper wouldn't have been published in just Scientific Reports.
      - phcordner 6y ago
        Okay man, cool. Let me know when your open-brain Dr. Mephisto trials disproving adult DA neurogenesis are written up in Nature Edit: the title’s not even misleading; “Parkinson’s” modifies “gene,” not “neurons” so it’s not even saying anything about the location of these neurons or when they are being created!
  - drewblaisdell 6y ago

phcordner 6y ago

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 6y ago
> 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 6y ago
  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.
  - gwerbret 6y ago
    To return the goal posts to their original location, my premise was that the title "Parkinson's gene may impair how new neurons are made throughout our lifetime" is misleading, as the neurons in question are not actually made throughout our lifetimes. The referenced paper, which uses zebrafish and a somewhat contrived cell culture model, does not provide any new evidence about actual dopaminergic neurogenesis in humans. It is fair to say that if they'd actually demonstrated such neurogenesis actually occurs, with or without PINK1, the paper wouldn't have been published in just Scientific Reports.
    - phcordner 6y ago
      Okay man, cool. Let me know when your open-brain Dr. Mephisto trials disproving adult DA neurogenesis are written up in Nature Edit: the title’s not even misleading; “Parkinson’s” modifies “gene,” not “neurons” so it’s not even saying anything about the location of these neurons or when they are being created!
- drewblaisdell 6y ago