Age-dependent, ovary-independent decrease in the nuclear binding kinetics of estrogen receptors in the brain of the mouse

Bélisle, Serge; Bellabarba, Diégo; Lehoux, Jean‐Guy

doi:10.1016/0002-9378(85)90077-8

Cited by 14 publications

(8 citation statements)

References 38 publications

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“…SD susceptibility was tested 3 weeks after ovariectomy with or without estrogen replacement (i.e., empty pellet implantation). The C57BL/6J background of FHM1 mutant mice has a gonadal hormone profile of aging very similar to that observed in menopausal women: prolonged cycles with delayed preovulatory rise of estrogen progress to acyclicity, lower estrogen levels, and hypergonadotrophic hypogonadism (91,92); decreased nuclear estrogen receptors and a nuclear translocation defect of estrogen-receptor complex have also been described as in humans (93)(94)(95).…”

Section: Figurementioning

confidence: 78%

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Eikermann-Haerter¹,

Dileköz²,

Kudo³

et al. 2008

J. Clin. Invest.

187

290

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Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the α 1A subunit of Ca v 2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

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Section: Figurementioning

confidence: 78%

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Eikermann-Haerter¹,

Dileköz²,

Kudo³

et al. 2008

J. Clin. Invest.

187

290

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“…It is conceivable that protection of some cochlear or central auditory tissue was provided by estrogen, but these effects were masked by ABR threshold elevation which was caused by diminution of hair cell integrity. Estrogen is known to affect neural systems in a variety of ways that can be neuroprotective/positive or (less commonly) neurotoxic/negative (e.g., Belisle et al, 1985;Bergman et al, 1989;Bittar et al, 2001;Easton et al, 2006;GarciaSegura et al, 2001;Papalexi et al, 2005;Picazo et al, 2003;Toran-Allerand et al, 1999;Usui, 2006), leaving open many possibilities to be addressed by future research. Various lines of evidence suggest that ovarian hormones may affect auditory function directly (Coleman et al, 1994;Hultcrantz et al, 2006).…”

Section: Sex Differences In Control (Non-exposed) Mice and The Effectmentioning

confidence: 99%

Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms

et al. 2006

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Gonadectomized and surgically intact adult C57BL/6J (B6) mice of both sexes were exposed for 12 hours nightly to a high-frequency augmented acoustic environment (AAE): repetitive bursts of a half-octave noise band centered at 20 kHz, 70 dB SPL. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (exhibited by B6 mice) were evaluated by obtaining auditory brainstem response thresholds at ages 3-, 6-, and 9-months; hair cell counts (cytocochleograms) were obtained at 9 months. A sex difference in the rate of genetic progressive hearing loss in B6 mice (observed by earlier studies) was confirmed, with females exhibiting a faster rate of threshold elevations and more severe loss of hair cells at age 9 months. Gonadectomy had no consistent effects on the rate or severity of hearing loss in nonexposed mice of either sex. An unexpected finding was that the high-frequency AAE treatment caused additional ABR threshold elevations and hair cell loss. In an earlier study, the same high-frequency AAE treatment on DBA/ 2J mice ameliorated hearing loss. The most severe AAE-induced losses occurred in surgically intact females, suggesting a potentiating effect of ovarian hormone(s).

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“…Interestingly, this inhibition has been found to be greater in aged animals (Belisle et al ., 1987). Although these observations are from uterus, similar phenomena may occur also in the central nervous system (Belisle et al ., 1985).…”

Section: Discussionmentioning

confidence: 83%

“…This is supported by previous findings demonstrating that prior to the onset of anestrous in rats, there is a decrease in the number of nuclear ER in the preoptic area (Wise & Camp, 1984). Interestingly, in the hypothalamic–pituitary axis, the baseline concentration of cytosolic ERs remained constant throughout aging, whereas ER nuclear sites decreased to an undetectable level (Belisle et al ., 1985). Our results indicate that there was a redistribution of ERαs from nucleus to cytoplasm in the cholinergic neurons of the MSVDB, i.e.…”

Section: Discussionmentioning

confidence: 99%

The effect of aging on the subcellular distribution of estrogen receptor‐alpha in the cholinergic neurons of transgenic and wild‐type mice

Kalesnykas

Roschier

Puoliväli

et al. 2005

Eur J of Neuroscience

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The degeneration of the basal forebrain cholinergic system plays an important role in cognitive deterioration in aging and Alzheimer's disease. Brain cholinergic neurons and their projections are affected by changes in the circulating levels of estrogens, which exert their effects mainly through the estrogen receptors. In this study, we investigated the effect of aging, estrogen status and transgenic genotype on the number of cholinergic neurons and the estrogen receptor alpha (ERalpha) content in the medial septum-vertical limb of the diagonal band of Broca. We used 6- and 12-month-old female double transgenic mice carrying mutated human amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E), and their nontransgenic littermate controls, which had been sham-operated or ovariectomized at the age of 3 months. Brain sections were double immunostained for choline acetyltransferase (ChAT) and ERalpha and used for stereological cell counting. We found that the number of ChAT-immunoreactive (ir) neurons containing nuclear ERalpha-ir was significantly lower in 12- than in 6-month-old mice. However, the age of the mice, the transgenic genotype or ovariectomy had no effect on the total number of ChAT-ir neurons, or on the number and percentage of all ChAT-ir neurons that contained ERalpha. These results indicate that aging is associated with translocation of ERalphas from the nucleus to the cytoplasm. We propose that this phenomenon is linked to those age-related processes known to be involved in inhibiting ERalpha binding to nuclei.

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Age-dependent, ovary-independent decrease in the nuclear binding kinetics of estrogen receptors in the brain of the mouse

Cited by 14 publications

References 38 publications

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1

Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms

The effect of aging on the subcellular distribution of estrogen receptor‐alpha in the cholinergic neurons of transgenic and wild‐type mice

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