Functional alterations of the nigrostriatal dopamine system in estrogen receptor-alpha knockout (ERKO) mice.
Estrogen represents an important factor for the development and function of the nigrostriatal dopamine system. Estrogen also controls sex-specific differentiation and activity of the nigrostriatal dopaminergic system. We used an estrogen receptor-alpha knockout (-/-) model (ERKO) to study the influence of this particular receptor subtype on the regulation of functional characteristics of the male and female nigrostriatal dopamine system. On the striatal level, we found a sex-specific regulation of dopamine D1 receptors (D1) and dopamine receptor-interacting protein 78 (Drip78). In female (-/-) mice D1 receptor expression levels were increased compared to wild type (wt) animals, whereas in male (-/-) mice Drip78 mRNA levels were decreased compared to wt. In the midbrain, expression of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) was reduced in (-/-) mice of both sexes. Glial cell line-derived neurotrophic factor (GDNF) expression was not affected. These data demonstrate that the integrity of estrogen receptor-alpha (ERalpha) signalling is necessary for the regulation of gene expression of proteins known to be important for the function of the nigrostriatal system at the postsynaptic striatal and presynaptic midbrain level.
Küppers
Eva
E
Institute of Anatomy, University of Tübingen, D-72076 Tübingen, Germany.
Krust
Andre
A
Chambon
Pierre
P
Beyer
Cordian
C
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics; D013378:Substantia Nigra / Q000378:metabolism* / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C532098:Drip78 protein, mouse; D047628:Estrogen Receptor alpha; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008565:Membrane Proteins; D017447:Receptors, Dopamine D1; D014446:Tyrosine 3-Monooxygenase; D007041:Hypoxanthine Phosphoribosyltransferase; D004298:Dopamine