Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death

Zhang, Lei; Li, Beng shing; Zhao, Weqing; Chang, Yoong Hee; Ma, Wu; Dragan, Magdalena; Barker, Jeffery L.; Hu, Qian; Rubinow, David R.

doi:10.1016/s0169-328x(02)00130-4

Cited by 59 publications

(52 citation statements)

References 42 publications

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“…28 Furthermore, recent studies have indicated that local microvasculature and neural interactions in the brain are different between women and men. 29,30 These biological differences might cause different responses to ischemic injury, leading to more severe neurological deficits in women than in men.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke

Irie

Kamouchi

Hata

et al. 2015

Stroke

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Stroke is a major cause of long-term disability and death worldwide.1 Previous studies seemed to converge on the higher likelihood of poststroke disability in women than in men. [2][3][4][5][6][7][8][9][10] Because women have a longer life expectancy and the stroke incidence increases in older age groups, poststroke disability in women can become an important public health problem in many aging societies. 8 The reasons for sex differences in stroke outcomes remain unclear. Stroke characteristics and risk factors were shown to differ between women and men, 7,8 and these are probably underlying the differences in clinical outcomes. In addition, some studies indicated that medical management before and after stroke differed by sex. 3,10,11 If the differences are caused by insufficient medical management, the quality of care is important to reduce the sex differences in the functional outcome post stroke. However, if biological sex itself were a risk of poor functional outcome, a sex-specific strategy for stroke prevention would be needed.Accurate data on possible confounders are needed to elucidate whether sex differences in stroke outcomes result from background differences or there truly exist biological differences among the sexes in response to stroke. Moreover, to prove the generalizability, sex differences should be confirmed in different cohorts in the world because lifestyle, social environment, and healthcare systems are different depending on ethnic groups and countries. However, previous studies have been performed mainly in Europe and North America, and paucity of data from other parts of the world has been highlighted. 8Background and Purpose-Variable sex differences in clinical outcomes after stroke have been reported worldwide. This study aimed to elucidate whether sex is an independent risk factor of poor functional outcome after acute ischemic stroke. Methods-Using the database of patients with acute stroke registered in the Fukuoka Stroke Registry in Japan from 1999 to 2013, 6236 previously independent patients with first-ever ischemic stroke who were admitted within 24 hours of onset were included in this study. Baseline characteristics were assessed on admission. Study outcomes included neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin Scale score, 3-6 at discharge). Logistic regression analyses were performed to evaluate the association between sex and clinical outcomes. Results-Overall, 2398 patients (38.5%) were women. Severe stroke (National Institutes of Health Stroke Scale score, ≥8)on admission was more prevalent in women than in men. The frequency of neurological improvement or deterioration during hospitalization was not different between the sexes. After adjusting for possible confounders, including age, stroke subtype and severity, risk factors, and poststroke treatments, it was found that female sex was independently associated with poor functional outcome at discharge (odds ratio, 1.30; 95% confidence interval, 1.08-1.57). There was h...

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke

Irie

Kamouchi

Hata

et al. 2015

Stroke

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“…In addition, astrocytes, which modulate neuronal activity (Theodosis and Poulain, 1999), are also a target of E 2 (Garcia-Segura et al, 1989;Tobet et al, 1994) and contain E 2 receptors (Hosli et al, 2001). Surprisingly, in contrast to the proliferative and MAPK-stimulating effects of E 2 in neurons, Zhang et al (2002) observed that E 2 decreased cell proliferation in astrocytes, associated with downregulated ERK1/2, and increased cell death. If E 2 were to have the same effect in our mixed cultures, this may have led us to underestimate the extent of ERK1/2 activation.…”

Section: Is the Effect Of Estrogen Direct Or Mediated?mentioning

confidence: 95%

“…The mitogen-activated protein kinase (MAPK) pathway (Adams and Sweatt, 2002) has emerged as a major contributor to plasticity in vertebrates. A functional link between E 2 and the MAPK pathway has been established in non-neuronal (Migliaccio et al, 1996;Russell et al, 2000;de Jager et al, 2001) as well as in neuronal systems (Watters et al, 1997;Singer et al, 1999;Singh et al, 1999;Kuroki et al, 2000;Zhang et al, 2002). However, a direct involvement of E 2 and the MAPK pathway in plasticity has been described only in the hippocampus (Bi et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Morphological Effects of Estrogen on Cholinergic NeuronsIn VitroInvolves Activation of Extracellular Signal-Regulated Kinases

Dominguez¹,

Jalali²,

Lacalle³

2004

J. Neurosci.

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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 17␤-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.

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“…Alternate explanations include sex-based differen- tial activation of the MAPK pathway, differential sensitivity to estradiol-mediated suppression of the MAPK pathway (correlating with differential rates of proliferation and apoptosis), and differential regulation of CREB, a growthregulating transcription factor. 5,19,28,64,69 In an intracranial xenograft model of glioblastoma, estradiol induced tumor cell apoptosis and promoted survival. 6 Although SEER data cannot provide further explanation for disparity in outcome based on sex, there is ongoing work reported in the literature to gain understanding of these differences.…”

Section: Characteristics and Demographicsmentioning

confidence: 99%

Treatment of pediatric Grade II spinal ependymomas: a population-based study

Lin

Jea

Melkonian

et al. 2015

PED

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OBJECT Grade II spinal cord ependymomas occurring in pediatric patients are exceptionally rare neoplasms. In this paper the authors use a national cancer database to determine patient demographics, treatment patterns, and associated outcomes of this cohort. METHODS The Surveillance Epidemiology and End Results (SEER) database was used to analyze subjects younger than 18 years with histologically confirmed diagnoses of Grade II spinal cord ependymoma from the years 1973 to 2008. Descriptive data on the demographic characteristics of this cohort and the associated treatment patterns are shown. The Kaplan-Meier method was used to estimate overall survival at 1, 2, 5, and 10 years. RESULTS This cohort comprised 64 pediatric subjects with Grade II spinal ependymoma. The median age was 13 years, nearly half of the patients were male, and most were white (84%). The median follow-up was 9.2 years. Overall survival at 5 and 10 years was 86% and 83%, respectively. Gross-total resection was achieved in 57% of subjects, and radiation therapy was administered to 36%. Radiation therapy was administered to 78% of subjects after subtotal resection but only to 19% of patients after gross-total resection; this difference was significant (p < 0.001). In a multivariate regression model analyzing sex, age at diagnosis, year of diagnosis, radiotherapy, and extent of resection, female sex was found to be an independent predictor of decreased mortality (HR 0.15 [95% CI 0.02–0.94], p = 0.04). CONCLUSIONS These data show long-term outcomes for pediatric patients with Grade II spinal ependymoma. Radiotherapy was more likely to be administered in cases of subtotal resection than in cases of gross-total resection. Female sex is associated with decreased mortality, while other demographic or treatment modalities are not.

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Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death

Cited by 59 publications

References 42 publications

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke

Morphological Effects of Estrogen on Cholinergic NeuronsIn VitroInvolves Activation of Extracellular Signal-Regulated Kinases

Treatment of pediatric Grade II spinal ependymomas: a population-based study

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