17 beta-Estradiol may affect vulnerability of striatum in a 3-nitropropionic acid-induced experimental model of Huntington's disease in ovariectomized rats.
The aim of present study was to clarify the role of female sex hormones in the development and course of neurodegenerative disease in an experimental model of Huntington's disease induced by 3-nitropropionic acid (NPA) (30 mg/kg intraperitoneally (i.p.)/day for 4 days) in ovariectomized rat. Gonadectomy prompted oxidative stress and cell death evaluated by the detection of caspase-3, whereas 3-nitropropionic acid enhanced the oxidative stress induced by ovariectomy and it triggered cell damage characterized by increases of LDH levels. These changes were prevented by administration of 17 beta-estradiol. Our findings suggested that: (i) ovariectomy induced oxidative stress and apoptosis in the brain; (ii) 3-nitropropionic acid exacerbated oxidative stress induced by ovariectomy and shifting cell to cell death; and (iii) 17 beta-estradiol administration decreased oxidative stress and cell death induced by ovariectomy and 3-nitropropionic acid. These results revealed that sex ovarian hormones play a important role in onset and development of neurodegenerative diseases, as well as neuroprotective effects of 17 beta-estradiol against the changes induced ovariectomy and ovariectomy plus 3-nitropropionic acid.
Túnez
Isaac
I
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Cordoba, Spain. fm2tufii@uco.es
Collado
Juan A
JA
Medina
Francisco J
FJ
Peña
José
J
Del C Muñoz
María
M
Jimena
Ignacio
I
Franco
Francisco
F
Rueda
Ignacio
I
Feijóo
Montserrat
M
Muntané
Jordi
J
Montilla
Pedro
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes
D003292:Convulsants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D004958:Estradiol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C015392:3-nitropropionic acid