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Effect of estrogen receptor agonists treatment in MPTP mice: evidence of neuroprotection by an ER alpha agonist.
Neuropharmacology. 2004 Dec; 47(8):1180-8.N

Abstract

Beneficial effects of 17 beta-estradiol (17 beta-E(2)) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine (DA) depletion are well documented but the mechanisms implicated are poorly understood. The present experiments investigated the effect of estrogen receptor (ER) agonists treatment in MPTP mice as compared to 17 beta-E(2). The agonists specific for each subtype were 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT) (ER alpha agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and Delta 3-diol (5-androsten-3 beta, 17 beta-diol, also known as 5-androstenediol, androstenediol or hermaphrodiol) (ER beta agonists). Biogenic amines were assayed by HPLC with electrochemical detection. 8 mg/kg of MPTP was administered to give a moderate depletion of striatal DA and its metabolite dihydroxyphenylacetic acid (DOPAC). Protection against MPTP-induced striatal DA and DOPAC depletion was obtained with PPT and 17 beta-E(2) but not with DPN or Delta 3-diol. The striatal dopamine transporter (DAT) was assayed by autoradiography with [(125)I]RTI-121-specific binding. A positive and significant correlation was observed between striatal DA concentrations and [(125)I]RTI-121-specific binding, suggesting that estrogenic treatment that prevented the MPTP-induced DA depletion also prevented loss of DAT. The effect of PPT suggests the implication of an ER alpha in the estrogenic neuroprotection against MPTP. Pointing out which ER is implicated in neuroprotection becomes helpful in designing more specific estrogenic drugs for protection of the aging brain.

Authors+Show Affiliations

Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, 2705 Laurier Boulevard, Quebec City, Que. G1V 4G2, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15567427

Citation

D'Astous, Myreille, et al. "Effect of Estrogen Receptor Agonists Treatment in MPTP Mice: Evidence of Neuroprotection By an ER Alpha Agonist." Neuropharmacology, vol. 47, no. 8, 2004, pp. 1180-8.
D'Astous M, Morissette M, Di Paolo T. Effect of estrogen receptor agonists treatment in MPTP mice: evidence of neuroprotection by an ER alpha agonist. Neuropharmacology. 2004;47(8):1180-8.
D'Astous, M., Morissette, M., & Di Paolo, T. (2004). Effect of estrogen receptor agonists treatment in MPTP mice: evidence of neuroprotection by an ER alpha agonist. Neuropharmacology, 47(8), 1180-8.
D'Astous M, Morissette M, Di Paolo T. Effect of Estrogen Receptor Agonists Treatment in MPTP Mice: Evidence of Neuroprotection By an ER Alpha Agonist. Neuropharmacology. 2004;47(8):1180-8. PubMed PMID: 15567427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of estrogen receptor agonists treatment in MPTP mice: evidence of neuroprotection by an ER alpha agonist. AU - D'Astous,Myreille, AU - Morissette,Marc, AU - Di Paolo,Thérèse, PY - 2004/01/16/received PY - 2004/07/27/revised PY - 2004/08/17/accepted PY - 2004/11/30/pubmed PY - 2005/2/11/medline PY - 2004/11/30/entrez SP - 1180 EP - 8 JF - Neuropharmacology JO - Neuropharmacology VL - 47 IS - 8 N2 - Beneficial effects of 17 beta-estradiol (17 beta-E(2)) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine (DA) depletion are well documented but the mechanisms implicated are poorly understood. The present experiments investigated the effect of estrogen receptor (ER) agonists treatment in MPTP mice as compared to 17 beta-E(2). The agonists specific for each subtype were 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT) (ER alpha agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and Delta 3-diol (5-androsten-3 beta, 17 beta-diol, also known as 5-androstenediol, androstenediol or hermaphrodiol) (ER beta agonists). Biogenic amines were assayed by HPLC with electrochemical detection. 8 mg/kg of MPTP was administered to give a moderate depletion of striatal DA and its metabolite dihydroxyphenylacetic acid (DOPAC). Protection against MPTP-induced striatal DA and DOPAC depletion was obtained with PPT and 17 beta-E(2) but not with DPN or Delta 3-diol. The striatal dopamine transporter (DAT) was assayed by autoradiography with [(125)I]RTI-121-specific binding. A positive and significant correlation was observed between striatal DA concentrations and [(125)I]RTI-121-specific binding, suggesting that estrogenic treatment that prevented the MPTP-induced DA depletion also prevented loss of DAT. The effect of PPT suggests the implication of an ER alpha in the estrogenic neuroprotection against MPTP. Pointing out which ER is implicated in neuroprotection becomes helpful in designing more specific estrogenic drugs for protection of the aging brain. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15567427/Effect_of_estrogen_receptor_agonists_treatment_in_MPTP_mice:_evidence_of_neuroprotection_by_an_ER_alpha_agonist_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390804002576 DB - PRIME DP - Unbound Medicine ER -