REGULATION OF MCSF RECEPTORS ON MICROGLIA IN THE NORMAL AND INJURED MOUSE CENTRAL-NERVOUS-SYSTEM - A QUANTITATIVE IMMUNOFLUORESCENCE STUDY USING CONFOCAL LASER MICROSCOPY

The macrophage colony-stimulating factor (MCSF) is a 40-76-kD glycopro tein that plays an important role in the activation and proliferation of microglia both in vitro and in injured neural tissue. Here, we exam ined the regulation of MCSF receptor (MCSFR) and MCSF in the normal an d injured mouse central nervous system (CNS) by using confocal laser m icroscopy, quantitative immunofluorescence, and reverse transcriptase- polymerase chain reaction (RT-PCR) techniques. Immunohistochemistry on fixed, Boating tissue sections demonstrated low to moderate MCSFR imm unoreactivity (MCSFR-IR) on microglia in the gray and white matter thr oughout the mouse CNS in the forebrain, brainstem, cerebellum, and spi nal cord. High levels of MCSFR-IR were restricted to the superficial l ayer of the spinal cord dorsal horn, substantia nigra, and area postre ma, a CNS region that lacks the blood-brain barrier. CNS injury led to a strong and specific increase in MCSFR-IR in the directly injured do rsal forebrain, in the cervical spinal cord (C2) after transection of the sensory, minor occipital nerve, and in the axotomized facial motor nucleus. Further investigation at the mRNA level in the facial nucleu s model showed that this increase was accompanied by a rapid induction of the transcript for MCSFR, with a peak 1-2 days after injury, but o nly a constitutive expression of MCSF-mRNA. In summary, although norma l levels of MCSF receptor in most microglia are low microglial activat ion is accompanied by a rapid and massive increase. In view of the con stitutive expression of MCSF, the early upregulation of the MCSF recep tor may play a central role in preparing these macrophage-related cell s to take part in the cellular response to CNS injury. (C) 1998 Wiley- Liss, Inc.