Time-course of the expression of inflammatory cytokines and matrix metalloproteinases in the striatum and mesencephalon of mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a dopaminergic neurotoxin.
Injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice results in a retrograde nigrostriatal dopaminergic pathway denervation and subsequent tissue reorganization. Since the role of inflammatory mediators after MPTP remains unclear, proinflammatory cytokine and matrix metalloproteinase (MMP) expression were evaluated by comparative RT-PCR during denervation and tissue reorganization following a single-dose of MPTP (40 mg/kg, s.c.) in young (8-week-old) mice. The time-course of denervation/reorganization was assessed through [(3)H]GBR-12935 binding on dopamine transporter and tyrosine hydroxylase immunohistochemistry. In the striatum, TNF-alpha, IL-1alpha, IL-1beta, IL-6 and MMP-9 mRNA expression peaked on day 1. In the ventral mesencephalon, cytokines (TNF-alpha, IL-1alpha, IL-1beta) and MMP-9 mRNA expression peaked on day 3. During tissue reorganization (day 6 through 16), the only change observed in the striatum consisted of IL-1alpha mRNA and protein overexpression together with MMP-2 downregulation. Whereas the early expression of proinflammatory cytokines and MMP might participate in the retrograde nigrostriatal denervation, the late component of IL-1alpha expression suggests a possible role for this cytokine in the subsequent striatal reorganization.
Hébert
Guillaume
G
INSERM U-394 "Neurobiologie Intégrative", Institut François Magendie, Bordeaux, France. guillaume.hebert@bordeaux.inserm.fr
Arsaut
Josette
J
Dantzer
Robert
R
Demotes-Mainard
Jacques
J
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004660:Encephalitis / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000502:physiology; D013378:Substantia Nigra / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016207:Cytokines; D050483:Dopamine Plasma Membrane Transport Proteins; D018836:Inflammation Mediators; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D012333:RNA, Messenger; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D014446:Tyrosine 3-Monooxygenase; D020782:Matrix Metalloproteinases; D004298:Dopamine