title: Involvement of estrogen receptors in the resveratrol-mediated increase in dopamine transporter in human dopaminergic neurons and in striatum of female mice.
abstract: Treatment with resveratrol (RSV) has been shown to protect vulnerable neurons after various brain injuries and in neurodegenerative diseases. The mechanisms for the effects of RSV in brain are not fully understood, but RSV may affect the expression of various gene products. RSV is structurally related to the synthetic estrogen, diethylstilbestrol so the effects of RSV may be gender-specific. Here we studied the role of RSV in the regulation of dopamine transporter (DAT) in the striatum using male and female mice. The basic levels of DAT in the striatum showed no sex difference, but the levels increased significantly by RSV (20 mg/kg i.p.) in female but not in male mice. Pretreatment of mice with the selective estrogen receptor (ER), ERα- and ERβ antagonist ICI 182,780, led to a complete block of RSV effect on DAT protein levels, suggesting that ERs are involved in the up-regulation of DAT by RSV. Similar data was also obtained in culture using human MESC2.10 and mouse SN4741 dopaminergic cells after treatment with RSV. Data further showed that RSV specifically induced gene transcription of DAT in the dopaminergic cells. These results show that estrogen receptors are involved in the up-regulation of DAT by RSV in the dopaminergic neurons, demonstrating a sex-dependent effect of RSV in the brain that may be of clinical importance. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors: Department of Experimental Biomedicine and Clinical Neuroscience, Division of Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, corso Tukory 129, IT-90134 Palermo, Italy.
authors: Valentina
authors: V
authors: Di Liberto
authors: Johanna
authors: J
authors: Mäkelä
authors: Laura
authors: L
authors: Korhonen
authors: Melania
authors: M
authors: Olivieri
authors: Timofey
authors: T
authors: Tselykh
authors: Annika
authors: A
authors: Mälkiä
authors: Hai
authors: H
authors: Do Thi
authors: Natale
authors: N
authors: Belluardo
authors: Dan
authors: D
authors: Lindholm
authors: Giuseppa
authors: G
authors: Mudò
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D051379:Mice; D011960:Receptors, Estrogen / Q000378:metabolism*; D000077185:Resveratrol; D012737:Sex Factors; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013267:Stilbenes; D000077267:Fulvestrant; D004958:Estradiol; D000077185:Resveratrol