QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 12, 2006, 26(15):4104-4110; doi:10.1523/JNEUROSCI.0222-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Szego, E. M. Articles by Ábrahám, I. M. Search for Related Content PubMed PubMed Citation Articles by Szego, E. M. Articles by Ábrahám, I. M.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Estrogen Induces Estrogen Receptor -Dependent cAMP Response Element-Binding Protein Phosphorylation via Mitogen Activated Protein Kinase Pathway in Basal Forebrain Cholinergic Neurons In Vivo

Éva M. Szeg,¹ Klaudia Barabás,¹ Júlia Balog,¹ Nóra Szilágyi,¹ Kenneth S. Korach,² Gábor Juhász,¹ and István M. Ábrahám¹

¹Neurobiology Research Group, Hungarian Academy of Sciences, Eötvös Loránd University, H-1117 Budapest, Hungary, and ²Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Correspondence should be addressed to Dr. István M. Ábrahám, Neurobiology Research Group, Hungarian Academy of Sciences, Pázmány st 1/c, H-1117 Budapest, Hungary. Email: abraham{at}dec001.geobio.elte.hu

In addition to classical genomic mechanisms, estrogen also exerts nonclassical effects via a signal transduction system on neurons. To study whether estrogen has a nonclassical effect on basal forebrain cholinergic system, we measured the intensity of cAMP response element-binding protein (CREB) phosphorylation (pCREB) in cholinergic neurons after administration of 17-estradiol to ovariectomized (OVX) mice. A significant time-dependent increase in the number of pCREB-positive cholinergic cells was detected after estrogen administration in the medial septum-diagonal band (MS-DB) and the substantia innominata (SI). The increase was first observed 15 min after estrogen administration. The role of classical estrogen receptors (ERs) was evaluated using ER knock-out mice in vivo. The estrogen-induced CREB phosphorylation in cholinergic neurons was present in ER knock-out mice but completely absent in ER knock-out mice in MS-DB and SI. A series of in vitro studies demonstrated that estrogen acted directly on cholinergic neurons. Selective blockade of the mitogen activated protein kinase (MAPK) pathway in vivo completely prevented estrogen-induced CREB phosphorylation in cholinergic neurons in MS-DB and SI. In contrast, blockade of protein kinase A (PKA) was effective only in SI. Finally, studies in intact female mice revealed levels of CREB phosphorylation within cholinergic neurons that were similar to those of estrogen-treated OVX mice. These observations demonstrate an ER-mediated nonclassical effect of estrogen on the cholinergic neurons and that these actions are present under physiological conditions. They also reveal the role of MAPK and PKA–MAPK pathway activation in nonclassical estrogen signaling in the basal forebrain cholinergic neurons in vivo.

Key words: steroid; ChAT; nongenomic; transgenic mice; signaling pathways; estrogen

---

Received Jan. 17, 2006; revised March 2, 2006; accepted March 9, 2006.

Correspondence should be addressed to Dr. István M. Ábrahám, Neurobiology Research Group, Hungarian Academy of Sciences, Pázmány st 1/c, H-1117 Budapest, Hungary. Email: abraham{at}dec001.geobio.elte.hu

This article has been cited by other articles:

				J. Iqbal, O. Latchoumanin, and I. J. Clarke Rapid in Vivo Effects of Estradiol-17{beta} in Ovine Pituitary Gonadotropes Are Displayed by Phosphorylation of Extracellularly Regulated Kinase, Serine/Threonine Kinase, and 3',5'-Cyclic Adenosine 5'-Monophosphate-Responsive Element-Binding Protein Endocrinology, December 1, 2007; 148(12): 5794 - 5802. [Abstract] [Full Text] [PDF]

				M. I. Boulware, H. Kordasiewicz, and P. G. Mermelstein Caveolin Proteins Are Essential for Distinct Effects of Membrane Estrogen Receptors in Neurons J. Neurosci., September 12, 2007; 27(37): 9941 - 9950. [Abstract] [Full Text] [PDF]

				C. Orikasa, Y. Kondo, and Y. Sakuma Transient Transcription of the Somatostatin Gene at the Time of Estrogen-Dependent Organization of the Sexually Dimorphic Nucleus of the Rat Preoptic Area Endocrinology, March 1, 2007; 148(3): 1144 - 1149. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help