Decreased inflammation and augmented expression of trophic factors correlate with MOG-induced neuroprotection of the injured nigrostriatal system in the murine MPTP model of Parkinson's disease

• Published in: International immunopharmacology 2009-06, Vol.9 (6), p.781-791
• Main Authors: Kurkowska-Jastrzębska, I., Bałkowiec-Iskra, E., Ciesielska, A., Joniec, I., Cudna, A., Zaremba, M.M., Członkowski, A., Członkowska, A.
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; Biological and medical sciences; Brain - drug effects; Brain - immunology; Brain - metabolism; Brain - pathology; CD4+ cells; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cytokines - drug effects; Cytokines - immunology; Cytokines - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; EAE; GDNF; Glycoproteins - immunology; Glycoproteins - metabolism; Inflammation - immunology; Inflammation - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; MPTP Poisoning - immunology; MPTP Poisoning - metabolism; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin-Oligodendrocyte Glycoprotein; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurodegeneration; Neurology; Neurons - drug effects; Neurons - immunology; Neurons - metabolism; Neuroprotection; Peptide Fragments - immunology; Peptide Fragments - metabolism; Pharmacology. Drug treatments; T cells
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2009.03.003

The response of the immune system during injury of the central nervous system may play a role in protecting neurons. We have previously reported that immunization with MOG 35–55 prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of the dopaminergic system promotes less dopamine depletion and less dopaminergic damage of neurons in mice. In this study, we evaluate the influence of MOG immunization on the inflammatory reaction that occurs at the place of injury. C57Bl male mice, 2 and 12 months old, received i.p. injections of MPTP (40 mg/kg) and some groups animals also received an additional injection with myelin oligodendrocyte glycoprotein (MOG) 35–55 in CFA 6 days before MPTP administration. MPTP caused a common inflammatory reaction characterized by microglial activation, infiltration of T cells into the substantia nigra and striatum and increased expression of mRNA encoding pro-inflammatory cytokines (IL-1β, TNFα, INFγ) and trophic factors (TGFβ, GDNF). MOG immunization prior to MPTP administration significantly diminished the microglial reaction and reduced the levels of infiltrating CD8+ lymphocytes. The number of CD4+ T cells remained at the same level as in the MPTP group. Expression of pro-inflammatory cytokines was diminished. The mRNA expression of GDNF was significantly higher in the MOG pretreated mice relative to the MPTP group, both in the 2 month old and 12 month old groups. Since MOG immunization prior to MPTP intoxication appears to prevent nigrostriatal injury, the observed decrease of inflammation and increase of GDNF mRNA expression in the injured areas might represent one of the mechanisms of observed neuroprotection.