Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of Comparative Neurology, 532(11), e70000. https://doi.org/10.1002/cne.70000 Ruth Fabian-Fine et al.
Points
- Myelinated glial cells play a critical role in neuronal waste clearance by engulfing cellular debris and channeling it into the lymphatic system, a process mediated by aquaporin-4 (AQP4) water channels.
- In spider neurons and the human hippocampus, glial cells form projections into neuronal somata to internalize waste. However, this process is impaired in Alzheimer’s disease due to hypertrophic myelination and structural abnormalities.
- The study identifies “gliaptosis” as the cell death caused by the failure of myelinated glial cells to maintain neuronal waste clearance, leading to neurodegeneration and spongiform abnormalities.
- The study highlights similarities in waste clearance mechanisms between spiders (e.g., Cupiennius salei) and humans, showing that failure of this system contributes to neurodegenerative pathologies in both.
- These findings provide insights into the role of macroglia in Alzheimer’s and other neurodegenerative disorders, emphasizing the potential for therapeutic strategies targeting glial cell function to mitigate disease progression.
Summary
This study investigates the role of myelinated glial cells in waste clearance from neurons, exploring both arachnid and human models. The authors present evidence that cellular debris in spider neurons is engulfed by myelin-forming ependymal glial cells, which form myelin-derived waste-internalizing receptacles. These specialized glial cells channel the waste into the lymphatic system, likely utilizing aquaporin-4 (AQP4)-mediated water channels. The study shows similar processes occur in the human hippocampus, where myelinated AQP4-immunoreactive ependymal cells form projections into neuronal somata, internalizing cellular debris. However, in Alzheimer’s disease, these processes are impaired due to hypertrophic myelination, leading to obstruction and depletion of neuronal cytoplasm into the ependymal cells. The structural impairment of these macroglial cells is associated with spongiform abnormalities typical of neurodegenerative diseases.
Using various histological and ultrastructural techniques, the study reveals that in both spiders and humans, the failure of macroglial cells to perform waste clearance results in cellular dysfunction and neurodegeneration. The authors term this phenomenon “gliaptosis,” referring to the cell death caused by the failure of myelinated glial cells to maintain proper neuronal function. Cupiennius salei, a highly specialized glial-canal system, clears cellular waste from neurons in the spider species. This system is impaired in the presence of neurodegenerative pathologies similar to those seen in humans, highlighting the conservation of waste clearance mechanisms across species. The study provides compelling evidence that similar myelinated glial systems may play a crucial role in clearing neuronal waste in human and animal models.
The findings suggest that the structural failure of these glial cells could drive neurodegeneration in both arachnids and humans. This novel insight into macroglia-mediated waste clearance offers a new perspective on the mechanisms behind neurodegenerative diseases. The study underscores the importance of understanding glial cell function and its impact on disease progression, particularly in Alzheimer’s and other neurodegenerative disorders.
Link to the article: https://onlinelibrary.wiley.com/doi/10.1002/cne.70000
References Fabian‐Fine, R., Weaver, A. L., Roman, A. G., Winters, M. J., & DeWitt, J. C. (2024). Myelinated glial cells: Their proposed role in waste clearance and neurodegeneration in arachnid and human brain. Journal of Comparative Neurology, 532(11), e70000. https://doi.org/10.1002/cne.70000
