Striatal TH-immunopositive fibers recover after an intrastriatal injection of 6-hydroxydopamine in golden hamsters treated with prednisolone: Roles of tumor necrosis factor-¦Á and inducible nitric oxide synthase in neurodegeneration

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• 作者：Sebastiá ; n Rodrí ; guez ^{sebastian.rodriguez1978@hotmail.com 8886965987@mail.ecc.u-tokyo.ac.jp} ; Kazuyuki Uchida ^{auchidak@mail.ecc.u-tokyo.ac.jp} ; Hiroyuki Nakayama ; ^{anakaya@mail.ecc.u-tokyo.ac.jp}
• 关键词：Golden hamster ; 6-Hydroxydopamine ; Striatal Recovery ; Activated microglia ; Prednisolone ; Minocycline ; TNF-¦Á ; iNOS
• 刊名：Neuroscience Research
• 出版年：2013
• 出版时间：May-June, 2013
• 年：2013
• 卷：76
• 期：1-2
• 页码：83-92
• 全文大小：4022 K

文摘

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-¦Á, 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-¦Á and iNOS.