title: Striatal TH-immunopositive fibers recover after an intrastriatal injection of 6-hydroxydopamine in golden hamsters treated with prednisolone: roles of tumor necrosis factor-α and inducible nitric oxide synthase in neurodegeneration.
abstract: Neuroinflammation has been implicated in the pathology of neurodegenerative processes such as Parkinson's disease (PD). Using the golden hamster (GH) 6-hydroxydopamine (6-OHDA) model, we investigated whether the attenuation of neuroinflammation influences the onset and progression of dopamine cell degeneration. 6-OHDA-injected GH received a treatment of minocycline (MINO), prednisolone (Pred) or a combination of minocycline and prednisolone (MINO+Pred). Immunohistochemistry for tyrosine hydroxylase (TH), Iba-1 and glial fibrillary acidic protein (GFAP) was used to evaluate lesions in the nigrostriatal axis and the amount of activated microglia and astroglia, respectively. RT-PCR was used to measure mRNA levels of cytokines and trophic neuroprotective factors. The three anti-inflammatory treatments dramatically reduced activated microglia in the nigrostriatal axis. In addition, TH-immunostaining showed that the positive areas in the ipsilateral striatum of either MINO or Pred groups were higher than that of control. However, only in Pred group this recovery was significant. mRNA measurements demonstrated lower levels of TNF-α, iNOS, BDNF and GDNF in Pred group when compared with controls. The results suggest that TH-immunopositive fibers have the ability to recover after 6-OHDA-induced toxicity of dopaminergic neurons, and this recovery may be due to a decrease in the microglial production of TNF-α and iNOS.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-8657, Japan. sebastian.rodriguez1978@hotmail.com
authors.forename: Sebastián
authors.initials: S
authors.lastname: Rodríguez
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D007276:Injections, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D016627:Oxidopamine; D011239:Prednisolone; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase