Restoration of injured motoneurons reduces microglial proliferation in the adult rat facial nucleus.

Abstract

In the axotomized facial nucleus (axotFN), the levels of choline acetyltransferase, vesicular acetylcholine transporter, and gamma amino butyric acid A receptor α1 are decreased, after which the microglia begin to proliferate around injured motoneuron cell bodies. We conjectured that an injury signal released from the injured motoneurons triggers the microglial proliferation in the axotFN. However, it is unclear whether the level of microglial proliferation is dependent on the degree of motoneuronal insult. In this study, we investigated the relationship between the extents of motoneuronal injury and microglial proliferation in a rat axotFN model. Administration of glial cell line-derived neurotrophic factor, N-acetyl L-cysteine, or salubrinal at the transection site ameliorated the increase in c-Jun and the reductions in levels of phosphorylated cAMP response element binding protein (p-CREB) and functional molecules in the injured motoneurons. Concurrently, the levels of the microglial marker ionized calcium-binding adapter molecule 1 and of macrophage colony-stimulating factor (cFms), proliferating cell nuclear antigen, and p-p38/p38 were significantly downregulated in microglia. These results demonstrate that the recovery of motoneuron function resulted in the reduction in microglial proliferation. We conclude that the degree of neuronal injury regulates the levels of microglial proliferation in the axotFN.