Estrogen down-regulates glial activation in male mice following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication.
Emerging evidence suggests beneficial effect of estrogen for Parkinson's disease (PD), yet the exact mechanisms implicated remain obscured. Activated glia observed in MPTP mouse model and in PD may participate in the cascade of deleterious events that ultimately leads to dopaminergic nigral neuronal death. In vitro studies demonstrate that estrogen can modify the microglial and astroglial expression of inflammatory mediator, such as cytokines and chemokines implicated in neuroinflammation and neurodegeneration. To determine whether estrogen-elicited neuroprotection in PD is mediated through glia, adult male C57Bl/6 mice were treated with 17beta-estradiol (E2) for a total of 11 days. Following 5 days of pretreatment with E2, they were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the sixth day. The brains were collected on day 11. Immunohistochemistry and quantitative study were used to assess the number of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra pars compacta (SNpc) and that of activated astrocytes and activated microglia in the SNpc and the striatum. Pretreatment with E2 decreased the loss of TH-IR nigral neurons and diminished the deficit of TH-IR striatal fibers triggered by MPTP. The neuroprotective effect of E2 was coincident with an attenuation of a glial response within the nigra and the striatum. These findings suggest that the neuroprotective effects of E2 evidenced in MPTP mouse model might mediate through an inhibition of reactive glia. However, direct neuroprotective effects of E2 upon TH-IR neurons cannot be excluded.
Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
Wanida
W
Tripanichkul
Kittisak
K
Sripanichkulchai
David I
DI
Finkelstein
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004967:Estrogens; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase