Expression of colony stimulating factor-1 receptor (CSF-1R) by CNS neurons in mice.

We report that neurons in the central nervous system express colony stimulating factor-1 receptor (CSF-1R) mRNA and protein and that the expression has regional specificity. The presence of CSF-1R in neurons was demonstrated by the use of four different types of antibodies to CSF-1R and the presence of CSF-1R mRNA by in situ hybridization using oligonucleotide probe. In the steady state in most areas of the brain, CSF-1R is weakly expressed in only a few neurons.

Expression of stem cell factor and c-kit receptor in neural cells after brain injury.

Previously it has been shown that c-kit receptor (c-kitR) and its ligand, stem cell factor (SCF), are expressed in the central nervous system. We have reported that SCF in cultures regulates mouse microglial function. Here we demonstrate that SCF/c-kitR signaling also takes place in situ.

Lipopolysaccharide induction of MARCKS-related protein and cytokine secretion are differentially impaired in microglia from LPS-nonresponsive (C3H/HeJ) mice.

Many events involved in activation of microglia and leukocytes by lipopolysaccharide (LPS) are mediated by protein kinase C (PKC), and we have recently demonstrated that a major PKC substrate, MARCKS-related protein (MRP), is selectively induced by LPS in murine microglia. In microglia from LPS-nonresponsive (C3H/HeJ) mice, induction of MRP and secretion of CSF-1 required much higher LPS concentrations (> or = 100 ng/ml) than in normal (C3H/OuJ) microglia (< or = 10 ng/ml). By contrast, TNF alpha production was not significantly increased in C3H/HeJ microglia even at 1 microgram LPS/ml.

Modulation of microglia by stem cell factor.

We reported previously that stem cell factor (SCF) is produced mainly by neurons and that its receptor (c-kitR), encoded by the protooncogene c-kit, is expressed in microglia, suggesting that SCF/c-kitR signaling may be involved in neuron-microglia interactions. We now report that SCF supports microglial survival in cultures, maintains them in process-bearing morphology, and inhibits microglial proliferation induced by colony stimulating factor-1. SCF potentiates microglial expression of the mRNAs of nerve growth factor, brain-derived neurotrophic factor and ciliary neurotrophic factor, and downregulates microglial expression of the inflammation-associated cytokines, tumor necrosis factor-a (TNF-alpha), and interleukin-1beta (IL-1beta).

Microglia and astroglia have a common progenitor cell.

Disaggregated neopallial cells from newborn C3H/HeJ mice were cloned in Grenier hybridoma tissue culture dishes, and culture wells that contained only one cell were marked. After 8-10 days of culturing, the cultures were fixed and double immunolabeled for microglia with Mac-1 antibody and for astroglia with antibody to GFAP. Each marked well containing a clone was identified as either a microglia, astroglia, mixed microglia-astroglia, or an unlabeled clone.