Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury.
The physiological reactions after spinal cord injury are accompanied by local synthesis of the transcriptional activator retinoic acid (RA). RA exerts its effects by binding to retinoic acid receptors (RAR) which heterodimerize with retinoid X receptors (RXR) and then act as ligand-activated transcription factors. To identify possible cellular targets of RA we investigated protein levels and cellular distribution of retinoid receptors in the rat spinal cord at 4, 7, 14 and 21 days after a contusion injury. In the nonlesioned spinal cord, immunoreactivity for RARalpha, RXRalpha, RXRbeta and RXRgamma was localized in the cytosol of neurons, that of RXRalpha and RXRbeta in astrocytes and that of RARalpha, RXRalpha and RXRgamma in some oligodendrocytes. After contusion injury RARalpha and all RXRs appeared in the cell nuclei of reactive microglia and macrophages. This nuclear staining began at 4 days, was most prominent at 7 and 14 days and had decreased at 21 days after injury. A similar nuclear translocation was also observed for the RARalpha, RXRalpha and RXRbeta staining in neurons situated around the border of the contusion. These observations suggest that RA participates as a signal for the physiological responses of microglia and neurons after CNS injury.
Schrage
Kirsten
K
Institute of Biology II, RWTH Aachen, Kopernikusstrasse 16, 52074 Aachen, Germany.
Koopmans
Guido
G
Joosten
Elbert A J
EA
Mey
Jörg
J
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D053331:Ectodysplasins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D018168:Receptors, Retinoic Acid / Q000145:classification / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism
D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; C489787:MAP2 protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018168:Receptors, Retinoic Acid; D048069:Tumor Necrosis Factors; C007293:DAPI; D014212:Tretinoin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases