![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, and Faculty of Pharmacy, Laval University, Quebec City, Quebec, Canada (M.D., M.M., T.D.P.); and Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain (P.M., L.M.G.-S.)
The present experiments sought to determine the implication of estrogen receptors (ER
and ER
) 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 pretreated for 5 days with 17-estradiol, an estrogen receptor (ER) agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT), or an estrogen receptor (ER) agonist, 5-androsten-3, 17-diol (
5-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 high-performance liquid chromatography, to 59% of control values; 17-estradiol and PPT but not 5-diol protected against this depletion. MPTP increased IGF-IR measured by Western blot, which was prevented by PPT. The phosphorylation of protein kinase B (Akt) (at serine 473), an essential mediator of IGF-I neuroprotective actions, increased after 17-estradiol and tended to increase with PPT but not with 5-diol treatments in MPTP mice. Glycogen synthase kinase 3 (GSK3) phosphorylation (at serine 9) was greatly reduced in MPTP mice; this was completely prevented by PPT, whereas 17-estradiol and 5-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 nonlesioned mice, 17-estradiol and PPT increased phosphorylation of striatal Akt and GSK3, whereas the other markers measured remained unchanged. 5-Diol increased GSK3 phosphorylation less than the PPT treatment. These results suggest that a pretreatment with estradiol promoted dopamine neuron survival by activating ER and increasing Akt and GSK3 phosphorylation.
Address correspondence to: Dr. Thérèse Di Paolo, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2. E-mail: therese.dipaolo{at}crchul.ulaval.ca
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
 |
 |
 |
|
 |
 |
 |
