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Updated: Aug 18, 2026
Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Intrathecal injection in MaFIA mouse model inflicts localized reduction of macrophage populations within the dorsal
Samuel B Chivers1, Cassandra L McLay1, Nathaniel A Jeske1,2,3
1Departments of Oral and Maxillofacial Surgery, Center for Pain Therapeutics and Addiction Research, University of Texas Health San Antonio, TX, USA.
Abstract:
Macrophages represent an essential component of the innate immune system that regulates multiple nervous system functions. This is highlighted in previous research that identifies an important somatosensory role for macrophages in peripheral dorsal root ganglia (DRG). In several pre-clinical pain models, DRG macrophage numbers increase with little evidence as to the origin. The objective of this work was to investigate this phenomenon with the innovative Macrophage Fas-Induced Apoptosis (MaFIA) mouse transgenic animal model and establish the source of macrophage expansion in a chronic intermittent hypoxia model. Intrathecal administration of AP20187 was performed in MaFIA mice to take advantage of the blood brain barrier impermeability of AP20187 and prevent exposure to systemic tissues in order to determine whether knocking down DRG tissue resident macrophages would alter hypoxia-related doubling of cell numbers in DRG. Localized AP20187 exposure to the central nervous system and adjacent DRG structures reduced macrophage in restricted neuronal tissues including spinal column and DRG without affecting macrophage populations in bone marrow, circulating blood, and sciatic nerve. Furthermore, MaFIA mice treated with AP20187 produced no increase in DRG macrophage cell numbers following exposure to chronic intermittent hypoxia. These findings indicate that targeted intrathecal administration of AP20187 reduces DRG tissue-resident macrophages and prevents chronic intermittent hypoxia-induced expansion of the innate immune cell population, negating a role for circulating monocytes in the phenomenon.
Insights
Researchers used the Macrophage Fas-Induced Apoptosis (MaFIA) mouse model to investigate macrophage origins in the nervous system. Targeted drug delivery prevented macrophage expansion in dorsal root ganglia during chronic intermittent hypoxia, indicating tissue-resident cells are responsible.
Area of Science:
- Neuroimmunology
- Innate Immune System
Background:
- Macrophages play a key role in nervous system functions, particularly in somatosensory pathways within dorsal root ganglia (DRG).
- Previous studies noted increased DRG macrophage numbers in preclinical pain models without identifying their origin.
Purpose of the Study:
- To investigate the source of macrophage expansion in DRG using the Macrophage Fas-Induced Apoptosis (MaFIA) mouse model.
- To determine if resident DRG macrophages contribute to the observed cell number increase during chronic intermittent hypoxia.
Main Methods:
- Utilized the MaFIA transgenic mouse model for targeted apoptosis induction.
- Administered AP20187 intrathecally to selectively eliminate central nervous system and DRG macrophages, leveraging blood-brain barrier impermeability.
- Exposed treated MaFIA mice to chronic intermittent hypoxia.
Main Results:
- Intrathecal AP20187 successfully reduced macrophage populations in the spinal column and DRG without affecting systemic sites like bone marrow or blood.
- MaFIA mice treated with AP20187 did not exhibit an increase in DRG macrophage numbers following chronic intermittent hypoxia exposure.
- These results demonstrate that circulating monocytes are not the source of hypoxia-induced DRG macrophage expansion.
Conclusions:
- Targeted intrathecal administration of AP20187 effectively reduces DRG tissue-resident macrophages.
- This targeted approach prevents the expansion of innate immune cells in DRG during chronic intermittent hypoxia.
- The findings negate a role for circulating monocytes in the observed DRG macrophage proliferation under hypoxic conditions.
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