Studying the Role of Microglia in Neurodegeneration and Axonal Regeneration in the murine Visual System
Alexander M Hilla1,2, Dietmar Fischer1,2
1Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Bochum, Germany.
Abstract:
Microglia reside in the central nervous system (CNS) and are involved in the maintenance of the physiologic state. They constantly survey their environment for pathologic alterations associated with injury or diseases. For decades, researchers have investigated the role of microglia under different pathologic conditions, using approaches aiming to inhibit or eliminate these phagocytic cells. However, until recently, methods have failed to achieve complete depletion. Moreover, treatments often affected other cells, making unequivocal conclusions from these studies difficult. Recently, we have shown that inhibition of colony stimulating factor 1 receptor (CSF1R) by oral treatment with PLX5622 containing chow enables complete depletion of retinal microglia and almost complete microglia depletion in the optic nerve without affecting peripheral macrophages or other cells. Using this approach, we investigated the role of microglia in neuroprotection in the retina and axon regeneration in the injured optic nerve under different conditions. Thus, this efficient, reliable and easy to use protocol presented here will enable researchers to unequivocally study the contribution of microglia on neurodegeneration and axon regeneration. This protocol can be also easily expanded to other paradigms of acute and chronic injury or diseases in the visual system.
Insights
Researchers developed a new method to deplete microglia, the immune cells of the central nervous system (CNS), enabling clearer studies on their role in neuroprotection and axon regeneration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are central nervous system (CNS) immune cells crucial for maintaining physiological state and detecting pathological changes.
- Previous methods for microglia depletion were often incomplete and affected other cell types, hindering research.
- Studying microglia's precise role in CNS health and disease has been challenging due to limitations in depletion techniques.
Purpose of the Study:
- To present a reliable and efficient protocol for microglia depletion in the CNS.
- To investigate the role of microglia in neuroprotection within the retina and axon regeneration in the injured optic nerve.
- To provide a method for unequivocally studying microglia's contribution to neurodegeneration and regeneration.
Main Methods:
- Utilized oral treatment with PLX5622-containing chow to inhibit colony-stimulating factor 1 receptor (CSF1R).
- Achieved complete depletion of microglia in the retina and near-complete depletion in the optic nerve.
- Ensured no significant impact on peripheral macrophages or other cell populations.
Main Results:
- Demonstrated successful and specific depletion of microglia using CSF1R inhibition.
- Established a robust protocol for studying microglia-dependent processes in the CNS.
- Showcased the utility of this method for investigating neuroprotection and axon regeneration.
Conclusions:
- Inhibition of CSF1R provides an effective and specific method for microglia depletion in the CNS.
- This protocol allows for unambiguous investigation into the functions of microglia in neuroprotection and axon regeneration.
- The presented method is adaptable for studying various acute and chronic injury models within the visual system and potentially other CNS areas.
