ADAM12 is expressed by astrocytes during experimental demyelination.
A disintegrin and metalloproteinase (ADAM) 12 represents a member of a large family of similarly structured multi-domain proteins. In the central nervous system (CNS), ADAM12 has been suggested to play a role in brain development, glioblastoma cell proliferation, and in experimental autoimmune encephalomyelitis. Furthermore, ADAM12 was reported to be almost exclusively expressed by oligodendrocytes and could, therefore, be considered as suitable marker for this cell type. In the present study, we investigated ADAM12 expression in the healthy and pathologically altered murine CNS. As pathological paradigm, we used the cuprizone demyelination model in which myelin loss during multiple sclerosis is imitated. Besides APC(+) oligodendrocytes, SMI311(+) neurons and GFAP(+) astrocytes express ADAM12 in the adult mouse brain. ADAM12 expression was further analyzed in vitro. After the induction of demyelination, we observed that activated astrocytes are the main source of ADAM12 in brain regions affected by oligodendrocyte loss. Exposure of astrocytes in vitro to either lipopolysaccharides (LPS), tumor necrosis factor alpha (TNFalpha), glutamate, or hydrogen peroxide revealed a highly stimulus-specific regulation of ADAM12 expression which was not seen in microglial BV2 cells. It appears that LPS- and TNFalpha-induced ADAM12 expression is mediated via the classic NFkappaB pathway. In summary, we demonstrated that ADAM12 is not a suitable marker for oligodendrocytes. Our results further suggest that ADAM12 might be implicated in the course of distinct CNS diseases such as demyelinating disorders.
Baertling
Fabian
F
Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
Kokozidou
Maria
M
Pufe
Thomas
T
Clarner
Tim
T
Windoffer
Reinhard
R
Wruck
Christoph J
CJ
Brandenburg
Lars-Ove
LO
Beyer
Cordian
C
Kipp
Markus
M
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072199:ADAM12 Protein; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016900:Neurofilament Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D003471:Cuprizone; D005904:Glial Fibrillary Acidic Protein; D005971:Glutamates; D008070:Lipopolysaccharides; D016900:Neurofilament Proteins; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C096115:Adam12 protein, mouse