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Down-regulation of microglial activity attenuates axotomized nigral dopaminergic neuronal cell loss.
Song, Dae-Yong; Yu, Ha-Nul; Park, Chae-Ri; Lee, Jin-Sook; Lee, Ji-Yong; Park, Byung-Gu; Woo, Ran-Sook; Han, Jung-Tae; Cho, Byung-Pil; Baik, Tai-Kyoung.
Affiliation
  • Song DY; Department of Anatomy and Neuroscience, Eulji University School of Medicine, 143-5, Yongdu-dong, 301-832 Jung-gu, Daejeon, Republic of KoreaKorea. jbl0719@naver.com.
BMC Neurosci ; 14: 112, 2013 Oct 04.
Article in En | MEDLINE | ID: mdl-24093518
BACKGROUND: There is growing evidence that inflammatory processes of activated microglia could play an important role in the progression of nerve cell damage in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease which harbor features of chronic microglial activation, though the precise mechanism is unknown. In this study, we presented in vivo and ex vivo experimental evidences indicating that activated microglia could exacerbate the survival of axotomized dopaminergic neurons and that appropriate inactivation of microglia could be neuroprotective. RESULTS: The transection of medial forebrain bundle (MFB) of a rat induced loss of dopaminergic neurons in a time-dependent manner and accompanied with microglial activation. Along with microglial activation, production of reactive oxygen species (ROS) was upregulated and TH/OX6/hydroethidine triple-immunofluorescence showed that the microglia mainly produced ROS. When the activated microglial cells that were isolated from the substantia nigra of the MFB axotomized animal, were transplanted into the substantia nigra of which MFB had been transected at 7 days ago, the survival rate of axotomized dopaminergic neurons was significantly reduced as compared with sham control. Meanwhile, when the microglial activation was attenuated by administration of tuftsin fragment 1-3 (microglia inhibitory factor) into the lateral ventricle using mini-osmotic pump, the survival rate of axotomized dopaminergic neurons was increased. CONCLUSION: The present study suggests that activated microglia could actively produce and secrete unfavorable toxic substances, such as ROS, which could accelerate dopaminergic neuronal cell loss. So, well-controlled blockade of microglial activation might be neuroprotective in some neuropathological conditions.
Subject(s)

Full text: 1 Database: MEDLINE Main subject: Reactive Oxygen Species / Microglia / Dopaminergic Neurons / Nerve Degeneration Limits: Animals Language: En Journal: BMC Neurosci Journal subject: NEUROLOGIA Year: 2013 Type: Article

Full text: 1 Database: MEDLINE Main subject: Reactive Oxygen Species / Microglia / Dopaminergic Neurons / Nerve Degeneration Limits: Animals Language: En Journal: BMC Neurosci Journal subject: NEUROLOGIA Year: 2013 Type: Article