Acute exposure to CNTF in vivo induces multiple components of reactive gliosis.
CNS trauma or disease induces a constellation of changes in the glia comprising the condition known as reactive gliosis. At present, little is known regarding the nature of the injury signals and the specific consequences of their actions. Ciliary neurotrophic factor (CNTF) induces acute phase proteins in liver and increases astrocytic glial fibrillary acidic protein (GFAP) both in vitro and in vivo. The purpose of the present study was to establish whether CNTF induces other aspects of gliosis. Between 10 and 72 h after 100 ng of recombinant human CNTF was administered into the adult rat neocortex, alterations were observed in a region extending several millimeters in circumference from the injection site. Microglia in this region were more apparent and astrocytes were hypertrophic. By in situ hybridization, mRNAs for GFAP, vimentin, and clusterin were upregulated when compared to the control hemisphere (which received heat-inactivated CNTF). By immunocytochemistry, GFAP, vimentin, glutathione-S-transferase mu, S-100, and OX-42 were elevated by 48 h. By contrast, the oligodendroglial marker GSTYp, the neuronal markers MAP-2 and NSE, the intermediate filament nestin, and the stress protein alpha B-crystallin were unchanged. In addition, a greater than twofold increase in the number of proliferating cells was observed. Since CNTF induces swelling and multiple "gliotic" genes in astrocytes, increases microglial number, and stimulates cell proliferation, we conclude that CNTF is sufficient to induce multiple aspects of gliosis. These data are consistent with a model whereby CNTF (which is synthesized by astrocytes) would be released when the integrity of the astrocyte membrane is compromised, whereupon it would elicit an inflammatory response.
Levison
S W
SW
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA. Slevison@Neuro.hmc.psu.edu
Ducceschi
M H
MH
Young
G M
GM
Wood
T L
TL
D000818:Animals; D001345:Autoradiography; D020934:Ciliary Neurotrophic Factor; D005260:Female; D005911:Gliosis / Q000139:chemically induced*; D006801:Humans; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger