Inhibition of thrombin‐induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo
The present study shows that activation of microglial NADPH oxidase and production of reactive oxygen species (ROS) is associated with thrombin‐induced degeneration of nigral dopaminergic neurons in vivo. Seven days after thrombin injection in the rat substantia nigra (SN), tyrosine hydroxylase immu...
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Published in | Journal of neurochemistry Vol. 95; no. 6; pp. 1755 - 1765 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.12.2005
Blackwell Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | The present study shows that activation of microglial NADPH oxidase and production of reactive oxygen species (ROS) is associated with thrombin‐induced degeneration of nigral dopaminergic neurons in vivo. Seven days after thrombin injection in the rat substantia nigra (SN), tyrosine hydroxylase immunocytochemistry showed a significant loss of nigral dopaminergic neurons. This cell death was accompanied by localization of terminal deoxynucleotidyl transferase‐mediated fluorecein UTP nick‐end labelling (TUNEL) staining within dopaminergic neurons. This neurotoxicity was antagonized by the semisynthetic tetracycline derivative, minocycline, and the observed neuroprotective effects were associated with the ability of minocycline to suppress NADPH oxidase‐derived ROS production and pro‐inflammatory cytokine expression, including interleukin‐1β and inducible nitric oxide synthase, from activated microglia. These results suggest that microglial NADPH oxidase may be a viable target for neuroprotection against oxidative damage. |
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Bibliography: | The present address of Dr Da Y. Lee is the Department of Pharmacology and Toxicology, University of Kansas, 5060 Malott Hall, 1251 Wescoe Hall Dr., Lawrence, KS 66045–7582, USA. The present address of Dr Sang H. Choi is the Brain Physiology and Metabolism Section, National Institute on Aging, NIH, Building 10, Room 6 N202, 10 Center Drive, Bethesda, MD 20892, USA. These two authors contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3042 1471-4159 |
DOI: | 10.1111/j.1471-4159.2005.03503.x |