ABSTRACT

Microglia have been generally accepted as brain macrophages and immunomodulator cells in the brain. For long time, these cells have been believed to induce, through the production of harmful factors, inflammation or neuronal degeneration in the pathologically damaged brain. We have found that the conditioned microglial medium (CMM) exhibits neurotrophic effects on the neocortical and mesencephalic neurons, implying that microglia produce certain neurotrophic molecules. To date, basic fibroblast growth factor (bFGF), plasminogen, and hepatocyte growth factor (HGF) have been identified as the effective molecules in microglial cells and their CMM. However, other additive neurotrophic molecules have also been suggested to be present in the CMM.

Previous analysis of neurotrophin mRNA by RT-PCR revealed that cultured microglia express nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) mRNA, and further suggested a possibility that the neurotrophins are released from the microglia. Therefore, we tested microglia`s ability to release neurotrophins in vitro. Rat primary microglia were found to constitutively secrete a limited amount of BDNF and NT-4/5, but NGF and NT- 3 were undetectable in the CMM. Stimulation of the cells with lipopolysaccharide (LPS) increased BDNF and NT- 4/5 secretion, and induced NGF secretion. Thus, this study demonstrated that microglia are able to secrete neurotrophins. For this reason, microglia are suggested to act as neurotrophic cells in the developing and pathological brain.