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Transitory disappearance of microglia during the regeneration of the lizard medial cortex
C Lopez-Garcia1, J Nacher, B Castellano
1Facultad de Ciencias Biologicas, Universidad de Valencia, Burjasot, Spain.
Abstract:
In normal lizards, microglial cells populate the medial cortex (a zone homologous to the hippocampal fascia dentata), with a preferential distribution along the border between the granular cell layer and the plexiform layers. Intraperitoneal injection of the neurotoxin 3-acetylpyridine (3AP) induces a selective lesion in the medial cortex with a rapid degeneration of the granular layer and its zinc-enriched axonal projection. Within 6-8 weeks, the granular layer is, however, repopulated by a new set of neurons generated in the subjacent ependyma and the cell debris is removed. The aim of this study was to determine to what extent microglia were involved in the scavenging processes during the regeneration process. To this end we studied the brains of regenerating lizards at different times after 3AP lesion, visualising microglial cells by the nucleoside diphosphatase (NDPase) histochemical reaction. Surprisingly, we found that stained microglial cells disappeared 6-8 hours after 3AP injection and remained absent until 10-15 days after injection. One month postlesion an increased population of microglial cells was found scattered throughout all plexiform layers of the cortex. Thorough examination of semithin and ultrathin sections confirmed the absence of microglia in the medial cortex of recent lesioned animals but the presence of an exuberant population after 1 month postlesion. In the tissue, phagocytotic scavenging was carried out by radial ependymocytes, not by microglia.
Insights
In lizards, microglia surprisingly disappear after a neurotoxin lesion, with radial ependymocytes clearing debris during medial cortex regeneration. Microglia reappear later, suggesting a non-traditional role in brain repair.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Microglial cells are key immune cells in the central nervous system.
- Lizard medial cortex is homologous to the hippocampal fascia dentata.
- Neurotoxin 3-acetylpyridine (3AP) causes selective medial cortex lesions.
Purpose of the Study:
- To investigate the role of microglia in the regeneration of the lizard medial cortex after 3AP-induced lesions.
- To determine if microglia are involved in clearing cellular debris during neural regeneration.
Main Methods:
- Histochemical visualization of microglial cells using nucleoside diphosphatase (NDPase) reaction.
- Analysis of lizard brains at various time points post-3AP injection.
- Examination of semithin and ultrathin tissue sections.
Main Results:
- Microglial cells were absent in the medial cortex 6-8 hours to 10-15 days after 3AP injection.
- An increased microglial population appeared one month post-lesion.
- Radial ependymocytes, not microglia, were responsible for phagocytotic scavenging of cell debris.
Conclusions:
- Microglia play a limited, delayed role in the acute phase of medial cortex regeneration in lizards.
- Radial ependymocytes are the primary phagocytic cells during early neural debris clearance in this model.
- This study reveals an unexpected mechanism of debris removal in neural regeneration.