Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sleep related changes in blood pressure in hypocretin-deficient narcoleptic mice.

ABSTRACT:

Study objectives

Although blood pressure during sleep and the difference in blood pressure between sleep and wakefulness carry prognostic information, little is known on their central neural mechanisms. Hypothalamic neurons releasing hypocretin (orexin) peptides control wake-sleep behavior and autonomic functions and are lost in narcolepsy-cataplexy. We investigated whether chronic lack of hypocretin signaling alters blood pressure during sleep.

Design

Comparison of blood pressure as a function of the wake-sleep behavior between 2 different hypocretin-deficient mouse models and control mice with the same genetic background.

Setting

N/A.

Subjects

Hypocretin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (TG, n = 12); hypocretin gene knock-out mice (KO, n = 8); congenic wild-type controls (WT, n = 10).

Interventions

Instrumentation with electrodes for sleep recordings and a telemetric blood pressure transducer.

Measurements and results

Blood pressure was significantly higher in either TG or KO than in WT during non-rapid eye movement sleep (NREMS; 4 ± 2 and 7 ± 2 mm Hg, respectively) and rapid eye movement sleep (REMS; 11 ± 2 and 12 ± 3 mm Hg, respectively), whereas it did not differ significantly between groups during wakefulness. Accordingly, the decrease in blood pressure between either NREMS or REMS and wakefulness was significantly blunted in TG and KO with respect to WT.

Conclusions

Chronic lack of hypocretin signaling may entail consequences on blood pressure that are potentially adverse and that vary widely among wake-sleep states.

SUBMITTER: Bastianini S

PROVIDER: S-EPMC3022942 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice.

Project description:Gene transfer has proven to be an effective neurobiological tool in a number of neurodegenerative diseases, but it is not known if it can correct a sleep disorder. Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Here, a replication-defective herpes simplex virus-1 amplicon-based vector was constructed to transfer the gene for mouse prepro-orexin into mice with a genetic deletion of the orexin gene. After in vitro tests confirmed successful gene transfer into cells, the gene vector was delivered to the lateral hypothalamus of orexin knockout (KO) mice where the orexin peptide was robustly expressed in the somata and processes of numerous neurons, and the peptide product was detected in the cerebrospinal fluid. During the 4-day life-span of the vector the incidence of cataplexy declined by 60%, and the levels of rapid eye movement sleep during the second half of the night were similar to levels in wild-type mice, indicating that narcoleptic sleep-wake behavior in orexin KO mice can be improved by targeted gene transfer.

| S-EPMC2615183 | biostudies-literature

Attention impairments and ADHD symptoms in adult narcoleptic patients with and without hypocretin deficiency.

Project description:BackgroundAttentional complaints are common in narcolepsy patients and can overlap with daytime sleepiness features. Few studies attempted to characterize attentional domains in narcolepsy leading to controversial results. We aimed to assess the impact of hypocretin deficiency on attentional functioning by comparing performances on the attention network test (ANT) of narcoleptic patients with hypocretin deficiency (narcolepsy type 1-NT1) versus patients without hypocretin deficiency (narcolepsy type 2-NT2) and healthy controls. We also addressed frequency and severity of psychopathological symptoms and their influence on performances on ANT.MethodsTwenty-one NT1 patients, fifteen NT2 patients and twenty-two healthy controls underwent the ANT, which allows assessing three separate attentional processes (alerting, orienting and executive control), and a psychometric assessment including questionnaires on attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, anxiety and depression symptoms.ResultsNT1 and NT2 patients presented with slower reaction times compared to controls. NT1 patients exhibited an impairment of alerting network relative to NT2 and healthy controls, while orienting and executive control networks efficiency were comparable between groups. NT1 and NT2 displayed higher severity of ADHD inattentive domain than controls, NT1 patients also displayed higher severity of ADHD hyperactive domain and depressive symptoms. In NT1, ADHD and depressive symptoms were positively correlated.ConclusionsDespite a shared slowing of reaction times in both NT1 and NT2, a selective impairment of alerting network was present only in hypocretin deficient patients. Clinicians should carefully consider attentional deficits and psychopathological symptoms, including ADHD symptoms, in the clinical assessment and management of patients with narcolepsy.

| S-EPMC5538711 | biostudies-literature

Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice.

Project description:Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT), also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM) sleep and cataplexy, which is a sudden loss of muscle tone during waking. It is still not known how HCRT regulates REM sleep or muscle tone since HCRT neurons are localized only in the lateral hypothalamus while REM sleep and muscle atonia are generated from the brainstem. To identify a potential neuronal circuit, the neurotoxin hypocretin-2-saporin (HCRT2-SAP) was used to lesion neurons in the ventral lateral periaquaductal gray (vlPAG). The first experiment utilized hypocretin knock-out (HCRT-ko) mice with the expectation that deletion of both HCRT and its target neurons would exacerbate narcoleptic symptoms. Indeed, HCRT-ko mice (n = 8) given the neurotoxin HCRT2-SAP (16.5 ng/23nl/sec each side) in the vlPAG had levels of REM sleep and sleep fragmentation that were considerably higher compared to HCRT-ko given saline (+39%; n = 7) or wildtype mice (+177%; n = 9). However, cataplexy attacks did not increase, nor were levels of wake or non-REM sleep changed. Experiment 2 determined the effects in mice where HCRT was present but the downstream target neurons in the vlPAG were deleted by the neurotoxin. This experiment utilized an FVB-transgenic strain of mice where eGFP identifies GABA neurons. We verified this and also determined that eGFP neurons were immunopositive for the HCRT-2 receptor. vlPAG lesions in these mice increased REM sleep (+79% versus saline controls) and it was significantly correlated (r = 0.89) with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency.

| S-EPMC2709920 | biostudies-literature

Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor.

Project description:To investigate the functional role of different alpha1-adrenergic receptor (alpha1-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the alpha1b-AR (alpha1b-/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the alpha1-AR subtypes in various tissues of alpha1b +/+ and -/- mice. Total alpha1-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the alpha1b -/- as compared with +/+ mice. Because of the large decrease of alpha1-AR in the heart and the loss of the alpha1b-AR mRNA in the aorta of the alpha1b-/- mice, the in vivo blood pressure and in vitro aorta contractile responses to alpha1-agonists were investigated in alpha1b +/+ and -/- mice. Our findings provide strong evidence that the alpha1b-AR is a mediator of the blood pressure and the aorta contractile responses induced by alpha1 agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in alpha1b -/- as compared with +/+ mice. In addition, phenylephrine-induced contractions of aortic rings also were decreased by 25% in alpha1b-/- mice. The alpha1b-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different alpha1-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.

| S-EPMC23548 | biostudies-literature

Sex-dependent compensatory mechanisms preserve blood pressure homeostasis in prostacyclin receptor-deficient mice.

Project description:Inhibitors of microsomal prostaglandin E synthase 1 (mPGES-1) are in the early phase of clinical development. Deletion of mPges-1 in mice confers analgesia, restrains atherogenesis, and fails to accelerate thrombogenesis, while suppressing prostaglandin E2 (PGE2), but increasing the biosynthesis of prostacyclin (PGI2). In low-density lipoprotein receptor-deficient (Ldlr-/-) mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its antiatherogenic effect. However, the effect of mPges-1 depletion on blood pressure (BP) in this setting remains unknown. Here, we show that mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr-/- mice, whereas, despite the direct vasodilator properties of PGI2, deletion of the I prostanoid receptor (Ipr) suppressed this response. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1-/- mice. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high-salt diet (HSD). This is attributable to the protective effect of estrogen in Ldlr-/- mice and in Ipr-/- Ldlr-/- mice. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In male mice, by contrast, the augmented formation of atrial natriuretic peptide (ANP) plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hence, men with hyperlipidemia on a HSD might be at risk of a hypertensive response to mPGES-1 inhibitors.

| S-EPMC8279587 | biostudies-literature

Persistence of circadian variation in arterial blood pressure in beta1/beta2-adrenergic receptor-deficient mice.

Project description:The beta-adrenergic pathway has been considered one important effector of circadian variation in arterial pressure. Experiments were performed in beta1/beta2-adrenergic receptor-deficient mice (beta1/beta2ADR-/-) to assess whether this pathway is required for circadian variation in mean arterial pressure (MAP) and to determine the impact of its loss on the response to changes in dietary salt. Twenty-four-hour recordings of MAP, heart rate (HR), and locomotor activity were made in conscious 16- to 17-wk-old mice [wild-type, (WT), n = 7; beta1/beta2ADR-/-, n = 10] by telemetry. Both WT and beta1/beta2ADR-/- mice demonstrated robust circadian variation in MAP and HR, although 24-h mean MAP was 10% lower (102.02 +/- 1.81 vs. 92.11 +/- 2.62 mmHg) in beta1/beta2ADR-/- than WT, HR was 16% lower and day-night differences reduced. Both WT and beta1/beta2ADR-/- mice adapted to changed salt intake without changed MAP. However, the beta1/beta2ADR-/- mice demonstrated a striking reduction in locomotor activity in light and dark phases of the day. In WT mice, MAP was markedly affected by locomotor activity, resulting in bimodal distributions in both light and dark. When MAP was analyzed using only intervals without locomotor activity, bimodality and circadian differences were reduced, and there was no significant difference between the two genotypes. The results indicate that there is no direct effect or role for the beta-adrenergic system in circadian variation of arterial pressure in mice, aside from the indirect consequences of altered locomotor activity. Our results also confirm that locomotor activity contributes strongly to circadian variation in blood pressure in mice.

| S-EPMC2386676 | biostudies-literature

Changes in total RNA in BK deficient mice after 4h sleep deprivation

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-31 | GSE132076 | GEO

Blood pressure dipping and sleep quality in the Wisconsin Sleep Cohort.

Project description:AimsNondipping blood pressure (BP) is associated with higher risk for hypertension and advanced target organ damage. Insomnia is the most common sleep complaint in the general population. We sought to investigate the association between sleep quality and insomnia and BP nondipping cross-sectionally and longitudinally in a large, community-based sample.MethodsA subset of the Wisconsin Sleep Cohort (n = 502 for cross-sectional analysis and n = 260 for longitudinal analysis) were enrolled in the analysis. Polysomnography measures were used to evaluate sleep quality. Insomnia symptoms were obtained by questionnaire. BP was measured by 24-h ambulatory BP monitoring. Logistic regression models estimated cross-sectional associations of sleep quality and insomnia with BP nondipping. Poisson regression models estimated longitudinal associations between sleep quality and incident nondipping over a mean 7.4 years of follow-up. Systolic and diastolic nondipping were examined separately.ResultsIn cross-sectional analyses, difficulty falling asleep, longer waking after sleep onset, shorter and longer total sleep time, lower sleep efficiency and lower rapid eye movement stage sleep were associated with higher risk of SBP and DBP nondipping. In longitudinal analyses, the adjusted relative risks (95% confidence interval) of incident systolic nondipping were 2.1 (1.3-3.5) for 1-h longer waking after sleep onset, 2.1 (1.1-5.1) for 7-8 h total sleep time, and 3.7 (1.3-10.7) for at least 8-h total sleep time (compared with total sleep time 6-7 h), and 1.9 (1.1-3.4) for sleep efficiency less than 0.8, respectively.ConclusionClinical features of insomnia and poor sleep quality are associated with nondipping BP. Our findings suggested nondipping might be one possible mechanism by which poor sleep quality was associated with worse cardiovascular outcomes.

| S-EPMC7882242 | biostudies-literature

Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy.

Project description:To determine whether hypocretin receptor gene (hcrtR1 and hcrtR2) expression is affected after long-term hypocretin ligand loss in humans and animal models of narcolepsy.Animal and human study. We measured hcrtR1 and hcrtR2 expression in the frontal cortex and pons using the RT-PCR method in murine models (8-week-old and 27-week-old orexin/ataxin-3 transgenic (TG) hypocretin cell ablated mice and wild-type mice from the same litter, 10 mice for each group), in canine models (8 genetically narcoleptic Dobermans with null mutations in the hcrtR2, 9 control Dobermans, 3 sporadic ligand-deficient narcoleptics, and 4 small breed controls), and in humans (5 narcolepsy-cataplexy patients with hypocretin deficiency (average age 77.0 years) and 5 control subjects (72.6 years).27-week-old (but not 8-week-old) TG mice showed significant decreases in hcrtR1 expression, suggesting the influence of the long-term ligand loss on the receptor expression. Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases. HcrtR2-mutated narcoleptic Dobermans (with normal ligand production) showed no alteration in hcrtR1 expression.Moderate declines in hcrtR expressions, possibly due to long-term postnatal loss of ligand production, were observed in hypocretin-ligand deficient narcoleptic subjects. These declines are not likely to be progressive and complete. The relative preservation of hcrtR2 expression also suggests that hypocretin based therapies are likely to be a viable therapeutic options in human narcolepsy-cataplexy.

| S-EPMC2542958 | biostudies-literature

Neurological Sleep Disorders and Blood Pressure: Current Evidence.

Project description:Hypertension is a major determinant of cardiovascular morbidity and mortality and is highly prevalent in the general population. While the relationship between sleep apnea and increased blood pressure has been well documented, less recognized is emerging evidence linking sleep-related movement disorders such as restless legs syndrome/periodic limb movements of sleep and sleep-related bruxism with blood pressure (BP) dysregulation and hypertension. There is also recent literature linking narcolepsy-cataplexy with elevated BP and altered pressor responses, and there are data suggesting abnormal BP control in rapid eye movement sleep behavior disorder. It is thought that neural circulatory mechanisms, sympathetic activation in particular, comprise the predominant mediator underlying elevated BP in these neurological sleep disorders. There is very limited evidence that treating these sleep disorders may be beneficial in lowering BP primarily because this question has received very little attention. In this review, we discuss the potential pathophysiologic mechanisms underlying elevated BP in restless legs syndrome/periodic limb movements of sleep, sleep-related bruxism, narcolepsy-cataplexy, and rapid eye movement sleep behavior disorder. We also examine the relationship between these sleep disorders and elevated BP and the impact of treatment of these conditions on BP control. Last, we discuss gaps in the literature evaluating the associations between these sleep disorders and elevated BP and identify areas for further research.

| S-EPMC6872192 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data