Time course of proliferation and elimination of microglia/macrophages in different neurodegenerative conditions.
Ablation of the hindlimb area of the sensorimotor cortex produces degeneration in the cortex (invasive traumatic injury) and leads to retrograde and/or anterograde degeneration in the thalamus (non-invasive injury, distal reaction). This provides an useful model to study the proliferation and elimination of microglia/macrophages in different neurodegenerative conditions. Changes in the morphology, distribution and numbers of microglia in the affected cortex and thalamus were analyzed at various time points (12 h to 30 days) after injury. In parallel, proliferation was determined by immunocytochemistry for the proliferating cell nuclear antigen and cell death by the TUNEL method. Proliferation was an early event in the microglia/macrophage response (from 12 h in the cortex and from 2 days post-lesion in the thalamus) and persisted up to 30 days. The different microglia/macrophage phenotypes proliferated in a specific temporospatial pattern. In the lesioned cortex, early activation and proliferation of intrinsic microglia was accompanied, from the second post-lesion day, by monocyte entrance and proliferation of monocyte-derived cells. In contrast, accumulation of cells in the thalamus resulted from proliferation of intrinsic microglia, without apparent/significant monocytic recruitment. During the subsequent microglia/macrophages removal the majority of the cells in the cortex transformed into ameboid cells devoid of cell processes that progressively accumulated as fully-developed macrophages tissue within the lesion (3-14 days) ultimately migrating out to the meningeal connective tissue (14-30 days). Only some process-bearing cells, remaining in the cortical tissue bordering the lesion, underwent degeneration by 14-21 days post-lesion. In contrast, in the distal affected thalamic nuclei, microglial cell death occurred by 14-30 days post-lesion. Altogether, this study shows that both the origin and fate of microglia/macrophages depend on the nature of the lesion.
Vela
José Miguel
JM
Department of Cell Biology, Physiology and Immunology, Unit of Histology, Faculty of Medicine, Autonomous University of Barcelona, Bellaterra, Spain.
Yáñez
Angela
A
González
Berta
B
Castellano
Bernardo
B
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000473:pathology; D008297:Male; D017628:Microglia / Q000166:cytology* / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D013003:Somatosensory Cortex / Q000166:cytology / Q000473:pathology; D013788:Thalamus / Q000166:cytology / Q000473:pathology