title: Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration.
abstract: The present study compared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced microglial activation in 3 different groups, sham-operated (SHM) mice, adrenalectomized mice (ADX), and ADX mice administered with corticosterone (ADX + CORT), to investigate the roles of glucocorticoids on microglial activation and dopaminergic neurodegeneration. Acute MPTP treatment induced moderate tyrosine hydroxylase (TH)-immunoreactive neuronal loss in the substantia nigra (SN) of SHM mice; this neuronal loss was significantly enhanced in ADX mice, but eventually recovered following the administration of corticosterone. Consistent with neuronal findings, acute MPTP treatment induced microglial activation in the SN from 1-3 days post injection in SHM mice. Interestingly, microglial activation was further enhanced and occasionally showed a phagocytic morphology in ADX mice that showed no circulating corticosterone. Furthermore, the activated microglia was significantly suppressed by the administration of corticosterone to ADX mice. Moreover, a confocal microscopic study demonstrated that the expression of inducible nitric oxide synthase protein, exclusively colocalized with activated microglia in the SN in ADX mice, was substantially decreased by the administration of corticosterone. Thus, the present study, using in-vivo adrenalectomy for a dopaminergic neurodegeneration model, successfully demonstrated the neuroprotective effects of corticosterone by microglial inhibition.
authors.affiliation: Department of Physiology, Nippon Medical School, Tokyo, Japan. sugama@nms.ac.jp
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.forename: Takato
authors.initials: T
authors.lastname: Takenouchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitani
authors.forename: Masayo
authors.initials: M
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D003345:Corticosterone / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000009:adverse effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D003345:Corticosterone