HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/R1328    most recent 90576.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Deurveilher, S. Articles by Semba, K. Search for Related Content PubMed PubMed Citation Articles by Deurveilher, S. Articles by Semba, K.

SLEEP AND BIOLOGICAL RHYTHMS

Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats

Departments of ¹Anatomy and Neurobiology, ²Psychology, ³Psychiatry, and ⁴Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

Submitted 7 July 2008 ; accepted in final form 21 August 2008

To understand how female sex hormones influence homeostatic mechanisms of sleep, we studied the effects of estradiol (E₂) replacement on c-Fos immunoreactivity in sleep/wake-regulatory brain areas after sleep deprivation (SD) in ovariectomized rats. Adult rats were ovariectomized and implanted subcutaneously with capsules containing 17β-E₂ (10.5 µg; to mimic diestrous E₂ levels) or oil. After 2 wk, animals with E₂ capsules received a single subcutaneous injection of 17β-E₂ (10 µg/kg; to achieve proestrous E₂ levels) or oil; control animals with oil capsules received an oil injection. Twenty-four hours later, animals were either left undisturbed or sleep deprived by "gentle handling" for 6 h during the early light phase, and killed. E₂ treatment increased serum E₂ levels and uterus weights dose dependently, while attenuating body weight gain. Regardless of hormonal conditions, SD increased c-Fos immunoreactivity in all four arousal-promoting areas and four limbic and neuroendocrine nuclei studied, whereas it decreased c-Fos labeling in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Low and high E₂ treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and locus coeruleus. The high E₂ treatment decreased c-Fos labeling in the VLPO under nondeprived conditions. These results indicate that E₂ replacement modulates SD-induced or spontaneous c-Fos expression in sleep/wake-regulatory and limbic forebrain nuclei. These modulatory effects of E₂ replacement on neuronal activity may be, in part, responsible for E₂'s influence on sleep/wake behavior.

ovariectomy; immunohistochemistry; orexin/hypocretin; tuberomammillary nucleus; ventrolateral preoptic nucleus