Hypoventilation and autonomic dysfunction in infant rats following orexin receptor blockade
| العنوان: | Hypoventilation and autonomic dysfunction in infant rats following orexin receptor blockade |
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| المؤلفون: | Jane R Kielhofner, Kevin J. Cummings |
| المصدر: | Revista Cubana de Investigaciones Biomédicas, Vol 38, Iss 5 (2020) |
| بيانات النشر: | Centro Nacional de Información de Ciencias Médicas. Editorial de Ciencias Médicas (ECIMED), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.medical_specialty, lcsh:R5-920, business.industry, Suvorexant, Sudden infant death syndrome, Biochemistry, Orexin receptor, Hypoventilation, Orexin, orexin, infant rats, control breathing, autonomic response, stress, Endocrinology, Control of respiration, Internal medicine, Genetics, medicine, Breathing, Wakefulness, medicine.symptom, business, lcsh:Medicine (General), Molecular Biology, Biotechnology |
| الوصف: | Introduction: Orexin (hypocretin) is a neuropeptide expressed by neurons in the lateral and perifornical hypothalamus that project widely to respiratory and autonomic regions of the brainstem. The activity of orexin neurons depends on vigilance state; they are most active in wakefulness, less active in quiet sleep, and silent during active sleep. Although there are well-described facilitatory effects of orexin in adult animals on the control of breathing and autonomic response to stress, its role in infancy has not been studied. This is an important issue because there is accumulating pathological evidence of orexinergic dysfunction in some cases of the Sudden Infant Death Syndrome (SIDS), a leading cause of death in infancy that is highly associated with abnormal respiratory and autonomic control during periods of sleep. We hypothesized that in infant (~2 week old) rat pups, orexin receptor blockade would: 1) lead to respiratory dysfunction, more so in wakefulness and quiet sleep than in active sleep, and 2) compromise the thermogenic response to mild environmental cooling. Objective: To study the effects of orexin in infant rats on the control of breathing and autonomic response to stress. Material an d Methods: To test these hypotheses we used whole-body plethysmography to monitor breathing and metabolic O 2 consumption in rat pups treated with suvorexant, a selective orexin 1 and 2 receptor antagonist. Vigilance state was determined using high-definition video to monitor and confirm standard behavioral criteria associated with quiet sleep, active sleep, and arousal in infant rat pups. Experiment 1: Pups cycled through wakefulness, quiet and active sleep for 1hr at thermoneutral ambient temperature (T A =31°C), at which point suvorexant (1mg/kg in 50% DMSO; n=3) or vehicle alone (n=2) was injected via an intra-abdominal cannula, and pups cycled between wakefulness and sleep for another 1 hr. The two groups were compared with respect to respiratory frequency (f), tidal volume (V T ), ventilation (V E ) and metabolic O 2 consumption (VO 2 ). Experiment 2: Pups were kept at thermoneutral T A for 1 hr, then exposed to a ~2°C drop in T A over the following 15 min, and then returned to baseline T A . Pups were then injected with either suvorexant (1mg/kg; n=8) or vehicle alone (n=8), and after another 1 hr, the T A challenge was repeated. In each animal, the change in metabolic O 2 consumption in response to cooling was measured before and after drug or vehicle injection. Results: In wakefulness and quiet sleep, suvorexant reduced respiratory frequency by 48 ± 4 breaths/min (~30%; p=0.01), and V E by 770 ± 254 ml/min/kg (~40%; p |
| اللغة: | Spanish; Castilian |
| تدمد: | 1561-3011 0864-0300 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a1960a09c1baec17ab2765a6134e560Test http://www.revibiomedica.sld.cu/index.php/ibi/article/view/464Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9a1960a09c1baec17ab2765a6134e560 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15613011 08640300 |
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