Early activation, motility, and homing of neonatal microglia to injured neurons does not require protein synthesis
- 19 May 2006
- Vol. 54 (1), 58-70
- https://doi.org/10.1002/glia.20355
Abstract
Neuronal injury in CNS tissues induces a rapid activation and mobilization of resident microglia (MG). It is widely assumed that changes in gene expression drive the morphological transformation of MG and regulate their mobilization during activation. Here, we used acutely excised neonatal rat brain slices to test whether the morphological transformation and homing of MG to injured neurons requires gene expression and de novo protein synthesis. Traumatic injury during excision of live brain tissue slices induces a rapid and transient translocation of a transcription factor, NF-κB, to nuclei in MG. This is followed within 4–8 h by an increase in immunolabeling for cell adhesion molecules and lysosomal proteins, accompanied by changes in cell morphology. Application of anisomycin, a protein synthesis inhibitor, prevents the increase in immunolabeling for markers of MG activation but not the morphological transformation. Confocal time-lapse imaging in live tissue slices indicates that MG cell motility (branch extension and retraction) and locomotion are unaffected by anisomycin at early postinjury time-points (<4 h), while at later time-points (4–8 h postinjury) MG locomotion but not motility is inhibited. Thus, activated MG rapidly localize to injured pyramidal neuron cell bodies by 4-h postinjury, even in the presence of anisomycin. Moreover, this early MG activation and homing to injured neurons is unaffected in tissue slices from β2 integrin deficient mice. These results indicate that gene activation and new protein synthesis coincide with, but are not necessary for, the rapid morphological transformation and early migration-dependent homing of activated MG to injured neurons in CNS tissues.Keywords
This publication has 55 references indexed in Scilit:
- Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in VivoScience, 2005
- Involvement of β1 integrin in microglial chemotaxis and proliferation on fibronectin: Different regulations by ADP through PKAGlia, 2005
- Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microgliaBrain Research Reviews, 2005
- Activation of Microglial Cells and Complement following Traumatic Injury in Rat Entorhinal-Hippocampal Slice CulturesJournal of Neurotrauma, 2004
- Identification of macrophage/microglia activation factor (MAF) associated with late endosomes/lysosomes in microglial cellsFEBS Letters, 2004
- IntegrinsCell, 2002
- Iba1 Is an Actin-Cross-Linking Protein in Macrophages/MicrogliaBiochemical and Biophysical Research Communications, 2001
- Prolonged Activation of NF-κB Following Traumatic Brain Injury in RatsJournal of Neurotrauma, 1999
- Development of microglia in the postnatal rat hippocampusHippocampus, 1998
- Lectin binding by resting and reactive microgliaJournal of Neurocytology, 1987