Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration.
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.
Sugama
Shuei
S
Department of Physiology, Nippon Medical School, Tokyo, Japan. sugama@nms.ac.jp
Takenouchi
Takato
T
Kitani
Hiroshi
H
Fujita
Masayo
M
Hashimoto
Makoto
M
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
D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D003345:Corticosterone