Regulation of connexin-43, GFAP, and FGF-2 is not accompanied by changes in astroglial coupling in MPTP-lesioned, FGF-2-treated parkinsonian mice.
Basic fibroblast growth factor (bFGF; FGF-2) has potent trophic effects on developing and toxically impaired midbrain dopaminergic (DAergic) neurons which are crucially affected in Parkinson's disease. The trophic effects of FGF-2 are largely indirect, both in vitro and in vivo, and possibly involve intermediate actions of astrocytes and other glial cells. To further investigate the cellular and molecular mechanisms underlying the restorative actions of FGF-2, and to analyse in more detail the changes within astroglial cells in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned striatum, we have studied striatal expression and regulation of connexin-43 (cx43), the principal gap junction protein of astroglial cells, along with the expression of glial fibrillary acidic protein (GFAP), FGF-2, and functional coupling. Our results show an immediate, yet transient increase in cx43 mRNA, and a sustained increase in FGF-2 mRNA, GFAP-positive cells, and cx43-immunoreactive punctata following the MPTP lesion, without any induction of functional coupling between astrocytes and other glial cells as revealed by dye coupling of patched cells. Unilateral administration of FGF-2 in a piece of gelfoam caused a further increase in cx43-positive punctata immediately adjacent to the implant, which was more pronounced than after application of a gelfoam containing the nontrophic control protein cytochrome C. These changes were parallelled by a small increase in cx43 protein determined by Western blot, but not by alterations in the coupling state of cells in the vicinity of the gelfoam implant. Although our data indicate that MPTP and exogenous FGF-2 may alter expression and protein levels of cx43, they do not support the notion that increases in cellular coupling may underly the trophic and widespread actions of FGF-2 in the MPTP-model of Parkinson's disease.
Rufer
M
M
Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
Wirth
S B
SB
Hofer
A
A
Dermietzel
R
R
Pastor
A
A
Kettenmann
H
H
Unsicker
K
K
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication / Q000187:drug effects; D002470:Cell Survival; D018031:Connexin 43 / Q000096:biosynthesis* / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D007546:Isoquinolines; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis
D018031:Connexin 43; D004343:Drug Implants; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C017475:lucifer yellow