title: Estrogen modulation of calretinin and BDNF expression in midbrain dopaminergic neurons of ovariectomised mice.
abstract: Estrogen attenuates the loss of dopamine neurons from the substantia nigra in animal models of Parkinson's disease (PD) and excitatory amino-acid induced neurotoxicity by interactions with brain-derived neurotrophic factor (BDNF), and calretinin (CR) containing dopaminergic (DA) neurons. To examine this interaction more closely, we treated the ovariectomised (OVX) mice with estrodial for 10days, and compared these mice to those OVX mice injected with the vehicle or control mice. Estrogen treatment in OVX mice had significantly more tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNpc). Dopamine transporter (DAT) mRNA and BDNF mRNA levels in the midbrain were also significantly increased by estrogen treatment (P<0.05). OVX markedly decreased the number of TH/CR double stained cells in the SNpc (P<0.05), a trend which could be reversed by estrogen treatment. However, the number of GFAP positive cells in the substantia nigra did not show significant changes (P >0.05) after vehicle or estrodial treatment. Furthermore, we found that estrogen treatment abrogated the OVX-induced decrease in the phosphorylated AKT (p-AKT), but not p-ERK. We hypothesize that short-term treatment with estrogen confers neuroprotection to DA neurons by increasing CR in the DA neurons and BDNF in the midbrain, which possibly related to activation of the PI3K/Akt signaling pathway.
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing, 400038, PR China; Chongqing City Family Planning Institute, Chongqing, 400020, PR China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, PR China. Electronic address: fanxiaotang2005@163.com.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
authors.affiliation: Southwest Hospital/Southwest Eye Hospital,Third Military Medical University, Chongqing, 400038, PR China. Electronic address: haiweixu2001@163.com.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D064032:Calbindin 2 / Q000096:biosynthesis* / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D010052:Ovariectomy; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D064032:Calbindin 2; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D051058:Oncogene Protein v-akt
keywords: BDNF; Calretinin; Estrogen; Parkinson; pAKT