Retinoic acid synthesis by a population of NG2-positive cells in the injured spinal cord.
Retinoic acid (RA) promotes growth and differentiation in many developing tissues but less is known about its influence on CNS regeneration. We investigated the possible involvement of RA in rat spinal cord injury (SCI) using the New York University (NYU) impactor to induce mild or moderate spinal cord contusion injury. Changes in RA at the lesion site were determined by measuring the activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at days 8-14 following the injuries. RALDH2 was the only detectable RALDH present in the control or injured spinal cord. The cellular localization of RALDH2 was identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected in oligodendroglia positive for the markers RIP and CNPase. Expression was also intense in the arachnoid membrane surrounding the spinal cord. After SCI the increase in RALDH2 was independent of the RIP- and CNPase-positive cells, which were severely depleted. Instead, RALDH2 was present in a cell type not previously identified as capable of synthesizing RA, that expressed NG2 and that was negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann cells and immature lymphocytes. We postulate that the RALDH2- and NG2-positive cells migrate into the injured sites from the adjacent arachnoid membrane, where the RALDH2-positive cells proliferate substantially following SCI. These findings indicate that close correlations exist between RA synthesis and SCI and that RA may play a role in the secondary events that follow acute SCI.
Mey
Jörg
J
Institute of Biology II, RWTH Aachen, Germany.
J Morassutti
Dante
D
Brook
Gary
G
Liu
Rong-Huan
RH
Zhang
Yi-Ping
YP
Koopmans
Guido
G
McCaffery
Peter
P
D000445:Aldehyde Oxidoreductases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050697:Retinal Dehydrogenase; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism* / Q000502:physiology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000445:Aldehyde Oxidoreductases; D000941:Antigens; D011509:Proteoglycans; D050697:Retinal Dehydrogenase; D014212:Tretinoin; D000099216:Chondroitin Sulfate Proteoglycan 4