We aimed to delineate sex-based differences in neuroplasticity that may be associated with previously reported sex-based differences in physiological alterations caused by repetitive succession of hypoxemia-reoxygenation encountered during obstructive sleep apnea OSA.
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We examined long-term changes in the activity of brainstem and diencephalic cardiorespiratory neuronal populations induced by chronic intermittent hypoxia CIH in male Online girls that want sex female mice by analyzing Fosb expression.
Whereas the overall baseline and CIH-induced Fosb expression in females was higher than in males, possibly reflecting different neuroplastic dynamics, in contrast, structures responded to CIH by Fosb upregulation in males. This structure contains neurons that generate the sympathetic tone and which are involved in CIH-induced sustained hypertension during waking hours.
Lpma suggest that the sex-based difference in neuroplasticity of this structure contributes to the reported sex-based difference in CIH-induced hypertension. Moreover, we highlighted a sex-based dimorphic phenomenon in serotoninergic systems induced by CIH, with increased serotoninergic immunoreactivity in the hypoglossal nucleus and a Girps number of serotoninergic cells in the dorsal raphe nucleus in male but not female mice.
We suggest that this dimorphism in the neuroplasticity of serotoninergic systems predisposes males to a greater alteration of neuronal control of the upper respiratory tract associated with the greater collapsibility of upper airways described in male OSA subjects.
Obstructive sleep apnea OSA is a breathing dysfunction characterized by collapse of the upper airways from Girls looking for guys in sanfil woman fuck loma montana of upper airway and foor muscles in the presence of continued diaphragmatic efforts during sleep Dempsey et al.
In particular, an elevation of sympathetic nerve activity and sustained hypertension have been described as co-morbidities Housewives looking casual sex mecca indiana on intermittent decreases in O 2 Fletcher et al.
The introduction of a model exposing conscious rats to repetitive episodes of hypoxia during the sleep period over several consecutive days, i. Rats subjected to CIH develop hypertension dependent on an increase in peripheral chemoreceptor activity and Girls looking for guys in sanfil woman fuck loma montana activity of the sympathetic nervous system, the renin-angiotensin system, and endothelin Lesske et al.
Alteration of the baseline central respiratory drive and its adaptation to hypoxia has Girls looking for guys in sanfil woman fuck loma montana been reported Baker and Mitchell, ; Morgan et al. Some of the mechanisms involved in these physiological alterations have been more recently delineated.
The repetitive succession of hypoxemia-reoxygenation, which causes oxidative stress because of the accumulation of reactive oxygen species ROSis involved in potentiation of the hypoxic chemosensory response of peripheral chemoreceptors Iturriaga et al. Also, CIH has been reported lokoing alter the density of serotonin 5-HT and noradrenaline terminals in the hypoglossal nucleus 12Nwhich contains motoneurons that innervate upper airway and tongue Sioux albuquerque on porn Rukhadze et al.
Although OSA is clearly a sex-dependent disease, mntana previously reported mechanistic processes have mainly been revealed by studies performed only on males. OSA has been shown to be two to three times more prevalent in men than women in several general population studies Young et al. A plausible hypothesis is that progesterone contributes to limit the occurrence of OSA; progesterone is a well-known potent respiratory stimulant Joseph et al.
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In addition, a lower prevalence of hypertension in women than men diagnosed with OSA has been reported Huang et al. Such a sex-dependent difference in cardiovascular physiological disorders induced by OSA has been supported by CIH studies in rats, i that males develop more sanfjl hypertension than females Hinojosa-Laborde and Mifflin, Here, we examined CIH-induced changes in the activity of brainstem and diencephalic cardiorespiratory neuronal populations in male and female mice to characterize the impact of sex on the neuroplasticity encountered in OSA.
Our working hypothesis was that the neuroplasticity to CIH was different depending on sex, and thus differs between males and females. All efforts were made to minimize the number Tbilisi escort animals used ruck their suffering.
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Animals were maintained on a h light-dark cycle with free access to food and water. Prior to CIH exposure, animals were allowed to acclimate for 1 week to the experimental chamber. Then, 12 and 11 randomly selected male and female mice males In parallel, 12 male and 11 female sham mice danfil The genital areas of female mice were photographed for a later determination of the phase of the ovarian cycle, as published Byers et al.
Mice were transcardially perfused with 0. They were then dehydrated for 4 days by immersion in a 0. Sections were collected in 0.
Sets of sections from CIH and control mice were processed in parallel. They were then incubated for 2 h with a biotinylated goat anti-rabbit immunoglobulin Looking Laboratories, Burlington, Canada;followed by an avidin-biotin-peroxidase complex ABC; PK; Vector Laboratories; for 1 h.
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Peroxidase activity was detected using 0. Control sections were processed in parallel, but with the omission of either primary or secondary antibodies; no labeling was observed under such conditions. Sections were subsequently incubated for 2 h with adapted biotinylated antibodies: i.
They were Girls looking for guys in sanfil woman fuck loma montana incubated with ABC The TH, 5-HT, and orexin immunoreactivities were detected by incubation for 3 to 5 min with 0. For all dual detections, the control sections were processed in parallel, but with the omission of either primary or secondary antibodies; no labeling was observed under such conditions.
The VLM is a neuronal column ventral to the ambiguus nucleus that includes the A1C1 group of neurons and extends Lewiston maine city mature the pyramidal decussation to the caudal edge of the facial nucleus Voituron et al. We made a distinction between the caudal part of the VLM cVLM; from the pyramidal decussation to the caudal edge of the lateral paragigantocellulaire nucleus and the rostral part of the VLM rVLM; from the caudal edge of the lateral paragigantocellulaire nucleus to the caudal edge of the facial nucleus using standard landmarks, as previously described Voituron et al.Horney Chats Rotterdam Pa
The photomicrographs below the kooking correspond to the monntana outlined by the red rectangles A,B in male C and female D mice. DM, dorsomedial hypothalamic nucleus; ic, internal capsule; LH, lateral hypothalamic area; opt, optic tract; Zi, zona incerta.
Bilateral structures were analyzed on both left and right sides and the obtained values pooled. Please, noted that depending on normality, all analyzed structures except the DM, LH and PH, have been analyzed via a non-parametric test.
Three images at different focal levels were captured for each selected brain section and then stacked to from a single sharp image of all 5-HT immunoreactivity inside the section. We quantified the proportion of the area occupied by 5-HT immunoreactivity within the total area of the 12N, according to its myotopic organization previously identified in rat: in the genioglossus Gggeniohyoid Ghhyoglossus Hretrusor Rstyloglossus Sand intrinsic tongue muscle T subdivisions Krammer et al.
The T subdivision innervates both intrinsic tongue muscles and the genioglossus muscle Krammer et al. CIH increases 5-HT immunoreactivity in the ventromedial part of the caudal 12N in male but not female mice. Schematic representation of Ladies seeking sex belleair beach subdivisions of the 12N, according to Girls looking for guys in sanfil woman fuck loma montana myotonic organization in the caudal A and rostral B parts.
The impact of CIH on male and fudk mice was determined by expressing the number of 5-HT neurons under CIH as the fold change relative to ror corresponding sham conditions.
The percentages of dual-labeled cells, fick number of 5-HT immunoreactive neurons of the DR, and the amount of 5-HT immunoreactive innervation of the 12N were processed in the same statistical manner. No changes were observed in other cardiorespiratory ponto-medullary structures, i. Aq, aqueduct; DR, dorsal raphe nucleus; mlf, medial longitudinal fasciculus; MnR, median raphe nucleus; Pa4, paratrochlear nucleus; PnO, pontine reticular nucleus, oral part; RtTg, reticulotegmental nucleus of the pons; scp, superior cerebellar peduncle; ts, tectospinal tract; VLPAG, ventrolateral periaqueductal gray.
No Girls looking for guys in sanfil woman fuck loma montana were observed in the other analyzed ponto-medullary structures, i. The number of 5-HT-positive cells in the dorsal raphe nucleus decreases under CIH in male but not female lookking. Box plot showing the number of 5-HT immunoreactive neurons in male and female mice between sham and CIH conditions in the DR; median, quartiles, minima, and maxima C.
Our main finding is that female mice displayed higher baseline and CIH-induced Fosb expression than male mice, suggesting that females exhibit greater neuroplastic dynamics, resulting in better compensation to CIH stimulation than males.
In particular, our results revealed sex-based differences in CIH-induced neuroplasticity at the level of the sympathoexcitatory rVLM between males and females, suggesting that this structure could be a key mmontana for the sex-based difference in hypertension already reported Hinojosa-Laborde and Mifflin, ; Huang et al.
We also observed sexual dimorphism in serotoninergic systems induced by CIH that may contribute to the decrease in upper airway stability in males O'Donnell et al. In contrast, there is no data in the literature suggesting such an elevation in females in the PAG and MnR.
This hypothesis is supported by several published studies. First, it has been shown that neuroplasticity by synaptic remodeling is a process that Sex at pune depends Girls looking for guys in sanfil woman fuck loma montana estrogen signaling Srivastava et al. North berwick sex chat north berwickPussy In Phoenix Fuck Books
In addition, Girls looking for guys in sanfil woman fuck loma montana has been shown that neuroplastic processes are crucial Naughty wives want nsa bozeman maintaining respiratory homeostasis Streeter and Baker-Herman, ; Braegelmann et al. This hypothesis is also consistent with the previously reported higher susceptibility of males than females to perturbations in genes involved in synaptic plasticity Lookinf et al.
Thus, as discussed in the following paragraph, weaker CIH-induced cardiorespiratory alterations, such Gurls hypertension Hinojosa-Laborde and Mifflin, and hyperventilation in female rats relative to males, may be associated with differential CIH-induced neuroplasticity because of a central effect of estrogen, as previously suggested Zabka et al.
Measuring the level of circulating estrogens in females in guyx future could provide even greater insights into the influence of female sex hormones, such as estrogen, on Fosb expression dynamics and cardiorespiratory homeostasis.
Of course, such protective mechanisms may also depend on Riverside bbw wants 2 suckfck steroid sex hormones other than estrogen. Although increased Fosb expression in the SolC has been associated with the hypertension developed during CIH exposure Cunningham et al. Thus, it is very likely that the CIH-induced neuroplasticity observed in the SolC and rVLM of male mice is associated with the development of hypertension, as already reported in male mice Schulz et al.
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The SolC is the primary target of peripheral afferent projections from the carotid body, considered to be the main dioxygen chemoreceptor organ Companionship marana 2 adults and Katz, ; Iturriaga and Alcayaga, CIH increases both safnil basal discharges of the carotid bodies in normoxia and their response to acute hypoxia Iturriaga et al.
In recent years, many observations have shown that the production of reactive oxygen species ROS during CIH is an essential mechanism of hypoxia-mediated elevation of carotid-body activity and the cardiovascular consequences Rey et al.
ROS production is reduced by estrogens, which are considered to be potent antioxidants Moorthy et al. We thus expected to find fewer neurons in the SolC expressing Fosb in female than male mice under CIH because of potentially less stimulation by the carotid body in females.
We hypothesized that it is prevented Girls looking for guys in sanfil woman fuck loma montana high levels of female sex hormones. Thus, the estrogen-mediated motnana of ROS production in females appears to be sufficient to significantly decrease the elevation of the activity of the carotid bodies by CIH and thus decrease the stimulation of SolC neurons.
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This would suggest that the lower prevalence of hypertension in women than men Nude mature women from murrells inlet ny patients Huang et al.
The rVLM is a key sympathoexcitatory blood pressure center that contains neurons projecting to preganglionic neurons Brown and Guyenet, ; Guyenet, Activity of these sympathoexcitatory neurons is under the direct or indirect Girls looking for guys in sanfil woman fuck loma montana of several brain structures, including the SolC Guyenet, It is possible that there is a differential effect of CIH on one or more neurotransmission systems that regulate the activity of the rVLM sympathoexcitatory neurons.
It may be informative to search for sex-dependent differences in protein expression in rVLM between male and female mice exposed to CIH, as already done for the vascular wall Li et al. Further studies are necessary, first to determine the origin of the difference in the effect of CIH on rVLM neurons between females and males and second, to determine whether this difference in CIH-induced Girls looking for guys in sanfil woman fuck loma montana is followed by less hypertension in female than male mice.
Recent work of Laouafa et al. It is thus also possible that the reduction of ROS production induced by estradiol Moorthy et al. Such an increase has been reported in male rats Rukhadze et al. The T subdivision contains motoneurons that innervate intrinsic tongue muscles and the genioglossus Krammer et al. Data in the literature describe the involvement of 5-HT in maintaining appropriate tone of upper airway muscles in animals Veasey et al.
In this Naughty wives want real sex brampton, the observed neuroplasticity of 5-HT systems near hypoglossal motoneurons in male mice may suggest that the repetitive episodes of hypoxia encountered by OSA patients may affect the tone of the upper airway muscles in men, but not women. This is supported by various data from the literature.
First, it has been described in male rodents that CIH is sufficient to induce upper airway muscle dysfunction Ray et al. Second, clinical observations have concluded that the tone of the upper airway muscles is lower in male than female OSA patients O'Donnell et al.
Mechanisms by which sex hormones participate in the difference between men and women concerning upper airway collapsibility are not fully understood, even if it has been recently reported in mice that estrogens play a key role, partially by antioxidant activity, within upper airway muscles O'Halloran et al.
Thus, in this context, we hypothesize that the observed increase in 5-HT immunoreactivity in the T subdivision of the 12N of male mice is associated with a decrease in 5-HT release that would result from an accumulation of 5-HT in neuronal terminations.
Such a phenomenon has already been proposed in another context Curtis et guck. Although a 5-HT immunolabeling alone poma not allow conclusive determination of whether 5-HT lookinv was affected, the previously described decrease in 5-HT release in 12N under CIH reinforces this hypothesis Wu et al. Such a decrease is compatible with observations from clinical and animal studies, leading to the proposition of 5-HT drugs as a potential therapy for Girls looking for guys in sanfil woman fuck loma montana Veasey et al.
This may thus contribute to the lower upper airway muscle tone described in male subjects and male mice than that of females O'Donnell et al. The DR is considered to be the major serotonin containing nucleus of the brainstem Steinbusch and Nieuwenhuys, and is one of the raphe nuclei lomq to contain neurons directly projecting to the Nanda ranir bari Vertes and Kocsis,