Estrogen reduces BDNF level, but maintains dopaminergic cell density in the striatum of MPTP mouse model.
Degeneration of dopaminergic (DA) axons in the striatum triggers upregulation of striatal trophic activity and striatal DA neuronal number in animal models of Parkinson's disease (PD). The present study investigated the effects of 17beta-estradiol (E2) on brain-derived neurotrophic factor (BDNF) expression and the density of DA neurons in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model in correlation with nigrostriatal DA innervation. Adult male C57Bl/6 mice were treated with E2 or vehicle for 11 days. Following 5 days of E2 or vehicle pretreatment, animals were injected with MPTP on day 6. On day 11, all mice were sacrificed, and the striatum were collected and processed for tyrosine hydroxylase (TH) and BDNF immunohistochemistry. Striatal TH-immunoreactive (IR) neurons were counted. Extent of DA innervation and BDNF expression in the striatum were assessed by measuring optical density of TH and BDNF immunoreactivity, respectively. Pretreatment with E2 partially prevented DA denervation and decreased striatal BDNF upregulation triggered by MPTP, but maintained the density of striatal TH-IR neurons to that observed in MPTP group. These findings suggest that estrogen protection of nigrostriatal DA axons against MPTP as well as preservation of the striatal TH-IR cell density in MPTP/E2 mice may be not mediated by BDNF.
Tripanichkul
Wanida
W
Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand. wanidatr@swu.ac.th
Gerdprasert
Orapin
O
Jaroensuppaperch
Em-orn
EO
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D004967:Estrogens; D018696:Neuroprotective Agents; D004298:Dopamine