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In the present study, we examined the ability of estrogen to enhance cholinergic neurite arborization in vitro and identified the signal transduction cascade associated with this effect. Basal forebrain primordia collected from rat pups on postnatal day 1 were cultured for 2 weeks and then treated with 5 nM 17β-estradiol for 24 hr. Cholinergic neurons were identified immunocytochemically with an antibody against the vesicular acetylcholine transporter and digitally photographed. Morphological analysis indicated that female cultures respond to estrogen treatment with an increase in total neurite length per neuron (4.5-fold over untreated controls) and in total branch segment number per neuron (2.3-fold over controls). In contrast, there was no change in total neurite length per neuron in male cultures, and we also observed a decrease in total branch segment number per neuron (0.5-fold below controls). Detailed histograms indicated that estrogen increases primary and secondary branch length and number and also increases terminal neuritic branches to the seventh order in female cultures. In a second set of experiments, we investigated the signal transduction cascade involved in this response, and found that an upstream extracellular signal-regulated kinase (ERK) inhibitor blocked the ability of estrogen to enhance outgrowth in female cultures. Our study provides strong evidence in support of the fact that the ERK pathway is required for estrogen-induced structural plasticity in the cholinergic system of female rats. Understanding the intracellular processes that underlie the response of cholinergic neurons to estrogen provides a necessary step in elucidating how cholinergic neurons can be particularly susceptible to degeneration in postmenopausal women.

Item Type:	Refereed Article
Keywords:	Estrogen, signal transduction, ERK, cholinergic, morphology
Research Division:	Biological Sciences
Research Group:	Zoology
Research Field:	Animal Cell and Molecular Biology
Objective Division:	Expanding Knowledge
Objective Group:	Expanding Knowledge
Objective Field:	Expanding Knowledge in the Biological Sciences
Author:	Dominguez, R (Dr Reymundo Dominguez)
ID Code:	122235
Year Published:	2004
Web of Science® Times Cited:	46
Deposited By:	Medicine (Discipline)
Deposited On:	2017-11-06
Last Modified:	2018-07-17
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