Influence of gonadal hormones on the behavioral effects of intermittent hypoxia in mice

Aubrecht, Taryn G.; Jenkins, Richelle; Magalang, Ulysses J.; Nelson, Randy J.

doi:10.1152/ajpregu.00379.2014

Cited by 9 publications

(11 citation statements)

References 46 publications

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“…Future experiments with DHT treatment may require a longer habituation phase to reduce the novelty aspect. Overall, these findings are consistent with literature demonstrating that both testosterone and estrogens are protective in the CNS and facilitate memory, while DHT can contribute to damaging processes on occasion (Aubrecht et al, 2014; Beer et al, 2006; Bimonte-Nelson et al, 2003; Frye et al, 2008; Osborne et al, 2009).…”

Section: Discussionsupporting

confidence: 91%

“…Whereas estrogens have been well established as protective against cardiovascular (dos Santos et al, 2014; Hinojosa-Laborde and Mifflin, 2005) and neurodegenerative disorders (Aubrecht et al, 2014; Gillies et al, 2004), the role of androgens is less defined (Aubrecht et al, 2014; Barron and Pike, 2012; Grimm et al, 2016; Holmes et al, 2013; Lau et al, 2014). Both estrogens and androgens can mediate rapid and long-term effects within the CNS, such as calcium signaling, increasing spine density within hippocampal regions or altering DNA transcription (Acaz-Fonseca et al, 2016; Cunningham et al, 2007; Handa et al, 2008; Jacome et al, 2016; Mahmoud et al, 2016; McEwen and Milner, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Androgens modulate chronic intermittent hypoxia effects on brain and behavior

Snyder

Duong

Trieu

et al. 2018

Hormones and Behavior

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Sleep apnea is associated with testosterone dysregulation as well as increased risk of developing neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). A rodent model of the hypoxic events of sleep apnea, chronic intermittent hypoxia (CIH), has been previously documented to impair cognitive function and elevate oxidative stress in male rats, while simultaneously decreasing testosterone. Therefore, androgens may modulate neuronal function under CIH. To investigate the role of androgens during CIH, male rats were assigned to one of four hormone groups: 1) gonadally intact, 2) gonadectomized (GDX), 3) GDX + testosterone (T) supplemented, or 4) GDX + dihydrotestosterone (DHT) supplemented. Each group was exposed to either normal room air or CIH exposure for one week, followed by memory and motor task assessments. Brain regions associated with AD and PD (entorhinal cortex, dorsal hippocampus, and substantia nigra) were examined for oxidative stress and inflammatory markers, key characteristics of AD and PD. Gonadally intact rats exhibited elevated oxidative stress due to CIH, but no significant memory and motor impairments. GDX increased memory impairments, regardless of CIH exposure. T preserved memory function and prevented detrimental CIH-induced changes. In contrast, DHT was not protective, as evidenced by exacerbated oxidative stress under CIH. Further, CIH induced significant spatial memory impairment in rats administered DHT. These results indicate androgens can have both neuroprotective and detrimental effects under CIH, which may have clinical relevance for men with untreated sleep apnea.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Androgens modulate chronic intermittent hypoxia effects on brain and behavior

Snyder

Duong

Trieu

et al. 2018

Hormones and Behavior

View full text Add to dashboard Cite

show abstract

“…Furthermore, our results demonstrated that reflex apneic responses and LVCF responses to stimulants in OVX + IH rats were significantly greater than those in all other groups ( Figures 2 , 4 ), suggesting that ovarian hormones exert a protective effect. This concept is further supported by previous studies showing that intact female animals are protected from IH-induced hypertension ( Hinojosa-Laborde and Mifflin, 2005 ) and impairment of spatial learning and memory ( Aubrecht et al, 2015 ); however, OVX removes this protection. The exact mechanism underlying the potentiating effect of OVX combined with IH exposure on LVCF sensitivity is unknown.…”

Section: Discussionsupporting

confidence: 66%

Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia

Huang

Yuan

Yang³

et al. 2018

Front. Physiol.

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Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen.

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“…Age and sex are two factors implicated in the prevalence of the disease, with men having two- to threefold greater risk for OSA compared to women, and for people older than 60 years having an AHI >15 is approximately 1.7-fold higher than middle-aged persons 6,7. The reason for the sex risk difference was initially explained by the protective role of progesterone and estrogens,8 as well as exposure to other risk factors in men such as fat deposition, smoking, and alcohol intake. The most probable explanation is that there are clear sex and age differences in the upper airway shape, genioglossal muscle activity, and craniofacial morphology, accounting for a higher male risk 9.…”

Section: Introductionmentioning

confidence: 99%

Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

Sforza¹,

Roche²

2016

117

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Obstructive sleep apnea (OSA) is a prevalent sleep disorder considered as an independent risk factor for cardiovascular consequences, such as systemic arterial hypertension, ischemic heart disease, cardiac arrhythmias, metabolic disorders, and cognitive dysfunction. The pathogenesis of OSA-related consequence is assumed to be chronic intermittent hypoxia (IH) inducing alterations at the molecular level, oxidative stress, persistent systemic inflammation, oxygen sensor activation, and increase of sympathetic activity. Overall, these mechanisms have an effect on vessel permeability and are considered to be important factors for explaining vascular, metabolic, and cognitive OSA-related consequences. The present review attempts to examine together the research paradigms and clinical studies on the effect of acute and chronic IH and the potential link with OSA. We firstly describe the literature data on the mechanisms activated by acute and chronic IH at the experimental level, which are very helpful and beneficial to explaining OSA consequences. Then, we describe in detail the effect of IH in patients with OSA that we can consider “the human model” of chronic IH. In this way, we can better understand the specific pathophysiological mechanisms proposed to explain the consequences of IH in OSA.

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Influence of gonadal hormones on the behavioral effects of intermittent hypoxia in mice

Cited by 9 publications

References 46 publications

Androgens modulate chronic intermittent hypoxia effects on brain and behavior

Androgens modulate chronic intermittent hypoxia effects on brain and behavior

Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia

Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

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