Expression of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in the perinatal, adult, and injured rat brain

Citation
A. Schober et al., Expression of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in the perinatal, adult, and injured rat brain, J COMP NEUR, 439(1), 2001, pp. 32-45
Citations number
31
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF COMPARATIVE NEUROLOGY
ISSN journal
00219967 → ACNP
Volume
439
Issue
1
Year of publication
2001
Pages
32 - 45
Database
ISI
SICI code
0021-9967(20011008)439:1<32:EOGDFI>2.0.ZU;2-W
Abstract
We and others have recently cloned a new member of the transforming growth factor-fi superfamily, growth differentiation factor-15/ macrophage inhibit ory cytokine-1 (GDF-15/MIC-1). Using in situ hybridization and immunohistoc hemistry, we determined the distribution of GDF-15/MIC-1 mRNA and protein i n the perinatal and cryolesioned adult rat brain. The choroid plexus epithe lium of all ventricles represents the site of strongest and almost exclusiv e mRNA expression in the normal perinatal and adult brain. The newborn rat brain reveals GDF-15/MIC-1 immunoreactivity (ir) in ependymal cells lining the ventricles, in the striatal subventricular zone, and in populations of nonneural cells of the thalamic/hippocampal lamina affixa, in addition to t hat in the choroid plexus. Unilateral cryogenic cortical lesioning induced a significant increase of GDF-15/MIC-1 mRNA expression and ir at the lesion site and expression in presumed neurons within the dorsal thalamic area. A t the lesion site, GDF-15/MIC-1-producing cells showed immuncytochemical fe atures of neurons, macrophages, and activated microglial cells. Flourescent microscopy revealed both intra- and extracellular GDF-15/MIC-1 ir. Up-regu lation of GDF-15/MIC-1 in activated macrophages (M phi) is also supported b y RT-PCR, ICC, and Western blot experiments showing pronounced induction of GDF-15/MIC-1 expression (mRNA and protein) in retinoic acid/phorbol ester- stimulated human M phi. Our data suggest that 1) GDF-15/MIC-1 is secreted i nto the cerebrospinal fluid and 2) in the newborn brain may penetrate throu gh the ependymal lining and act on developing neurons and/or glial cells. A s a constituent of cells in the lamina affixa, the protein might be involve d in the regulation of mesenchyme-epithelial interactions. Finally, GDF-15/ MIC-1 may also act within the antiinflammatory cytokine network activated i n CNS lesions. (C) 2001 Wiley-Liss, Inc.