title: Striatal GDNF Production Is Independent to Circulating Estradiol Level Despite Pan-Neuronal Activation in the Female Mouse.
abstract: Gender difference in Parkinson's disease (PD) suggests that female sex steroids may promote dopaminergic neuron survival and protect them from degeneration. The glial cell line-derived neurotrophic factor (GDNF) is believed to be dopaminotrophic; thus it is considered as a potential therapeutic target in PD. Additionally, GDNF is endogenously synthetized in the caudate/putamen of humans and striatum in rodents. A neuroprotective role of estrogens on the nigrostriatal pathway via the stimulation of GDNF has been proposed. Since the GDNF-producing parvalbumin (Parv) interneurons express the estrogen receptor alpha in the mouse striatum, we sought to determine whether ectopic estrogenic compound modulates the GDNF synthesis in mice. Using an ovariectomized-estradiol (E2) replacement regimen, which reliably generates a rise of plasma estradiol, we assessed the effects of different levels of E2 on the activation of striatal neuronal populations, and GDNF production. A strong correlation was found between plasma E2 and the expression of the immediate early gene cFos in the striatum, as well as in other cortical regions. However, moderate and high E2 treatments failed to induce any striatal GDNF mRNA and protein synthesis. High E2 only stimulates cFos induction in a low percentage of striatal Parv neurons whereas the majority of cFos-positive cells are medium spiny neurons. Activation of these projecting neurons by E2 suggests a role of circulating sex steroids in the modulation of striatal neural pathways.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Enterría-Morales
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Ivette
authors.initials: I
authors.lastname: López-López
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla, Sevilla, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: d'Anglemont de Tassigny
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D004958:Estradiol / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D007118:Immunoassay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D051100:Glial Cell Line-Derived Neurotrophic Factor; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D004958:Estradiol