MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on January 24, 2006; DOI: 10.1124/mol.105.018671

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.105.018671v1
69/4/1492    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by D'Astous, M.
Right arrow Articles by Di Paolo, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by D'Astous, M.
Right arrow Articles by Di Paolo, T.


Received for publication September 7, 2005.
Revised December 23, 2005.
Accepted for publication January 24, 2006.

Implication of the PI3K/Akt signaling pathway in the neuroprotective effect of estradiol in the striatum of MPTP mice

Myreille D'Astous 1, Pablo Mendez 2, Marc Morissette 1, Luis Miguel Garcia-Segura 2, Therese Di Paolo 1*

1 Molecular Endocrinology and Oncology Research Center, Laval University Medical Center 2 Instituto Cajal, C.S.I.C.

* Address correspondence to: E-mail: therese.dipaolo{at}crchul.ulaval.ca

Abstract

The present experiments sought to determine the implication of estrogen receptors (ER{alpha} and ER{beta}) and their interaction with insulin-like growth factor receptor (IGF-IR) signaling pathways in neuroprotection by estradiol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. C57Bl/6 male mice were pre-treated for 5 days with 17{beta} -estradiol, an estrogen receptor alpha (ER{alpha}) agonist, PPT (4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol) or an estrogen receptor beta (ER{beta}) agonist, {Delta}3-diol (5-androsten-3{beta}, 17{beta}-diol). On day 5, mice received MPTP (9 mg/kg) or saline injections and estrogenic treatments were continued for 5 more days. MPTP decreased striatal dopamine, measured by HPLC, to 59% of control values; 17{beta}-estradiol and PPT but not {Delta}3-diol protected against this depletion. MPTP increased IGF-IR measured by Western blot, which was prevented by PPT. The phosphorylation of Akt (at serine 473), an essential mediator of IGF-I neuroprotective actions, increased following 17{beta}-estradiol, tended to increase with PPT but not {Delta}3-diol treatments in MPTP mice. GSK3{beta} phosphorylation (at serine 9) was greatly reduced in MPTP mice; this was completely prevented by PPT whereas 17{beta}-estradiol and {Delta}3-diol treatments were less effective. The ratio between the levels of striatal Bcl-2 and BAD proteins, two apoptotic regulators, decreased after MPTP treatment. This effect was effectively prevented only in the animals treated with PPT. In non-lesioned mice, 17{beta}-estradiol and PPT increased phosphorylation of striatal Akt and GSK3{beta}, while the other markers measured remained unchanged. {Delta}3-diol increased GSK3{beta} phosphorylation less than the PPT treatment. These results suggest that a pre-treatment with estradiol promoted dopamine neuron survival by activating ER{alpha} and increasing Akt and GSK3{beta} phosphorylation.


Key words: Dopamine, Sex hormones, Protein Kinases (other), Phosphorylation/Dephosphorylation, Immunocytochemistry, Apoptosis, Excitotoxicity, neurodegeneration


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. R. Levin
Rapid signaling by steroid receptors
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1425 - R1430.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Alonso, M. Moreno, P. Ordonez, R. Fernandez, C. Perez, F. Diaz, A. Navarro, J. Tolivia, and C. Gonzalez
Chronic Estradiol Treatment Improves Brain Homeostasis during Aging in Female Rats
Endocrinology, January 1, 2008; 149(1): 57 - 72.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. R. Hammes and E. R. Levin
Extranuclear Steroid Receptors: Nature and Actions
Endocr. Rev., December 1, 2007; 28(7): 726 - 741.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Inoue, L. Lin, X. Lee, Z. Shao, S. Mendes, P. Snodgrass-Belt, H. Sweigard, T. Engber, B. Pepinsky, L. Yang, et al.
Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models
PNAS, September 4, 2007; 104(36): 14430 - 14435.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics