Post-sigh sleep apneas in mice: Systematic review and data-driven definition

Sleep apneas can be categorized as post-sigh (prevailing in non-rapid eye movement sleep) or spontaneous (prevailing in rapid eye movement sleep) according to whether or not they are preceded by an augmented breath (sigh). Notably, the occurrence of these apnea subtypes changes differently in hypoxic/hypercapnic environments and in some genetic diseases, highlighting the importance of an objective discrimination. We aim to: (a) systematically review the literature comparing the criteria used in categorizing mouse sleep apneas; and (b) provide data-driven criteria for this categorization, with the final goal of reducing experimental variability in future studies. Twenty-two wild-type mice, instrumented with electroencephalographic/electromyographic electrodes, were placed inside a whole-body plethysmographic chamber to quantify sleep apneas and sighs. Wake\u2013sleep states were scored on 4-s epochs based on electroencephalographic/electromyographic signals. Literature revision showed that highly different criteria were used for post-sigh apnea definition, the intervals for apnea occurrence after sigh ranging from 1 breath up to 20 s. In our data, the apnea occurrence rate during non-rapid eye movement sleep was significantly higher than that calculated before the sigh only in the 1st and 2nd 4-s epochs following a sigh. These data suggest that, in mice, apneas should be categorized as post-sigh only if they start within 8 s from a sigh; the choice of shorter or longer time windows might underestimate or slightly overestimate their occurrence rate, respectively

Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice

Early-life exposure to environmental toxins like tobacco can permanently re-program body structure and function. Here, we investigated the long-term effects on mouse adult sleep phenotype exerted by early-life exposure to nicotine or to its principal metabolite, cotinine. Moreover, we investigated whether these effects occurred together with a reprogramming of the activity of the hippocampus, a key structure to coordinate the hormonal stress response. Adult male mice born from dams subjected to nicotine (NIC), cotinine (COT) or vehicle (CTRL) treatment in drinking water were implanted with electrodes for sleep recordings. NIC and COT mice spent significantly more time awake than CTRL mice at the transition between the rest (light) and the activity (dark) period. NIC and COT mice showed hippocampal glucocorticoid receptor (GR) downregulation compared to CTRL mice, and NIC mice also showed hippocampal mineralocorticoid receptor downregulation. Hippocampal GR expression significantly and inversely correlated with the amount of wakefulness at the light-to-dark transition, while no changes in DNA methylation were found. We demonstrated that early-life exposure to nicotine (and cotinine) concomitantly entails long-lasting reprogramming of hippocampal activity and sleep phenotype suggesting that the adult sleep phenotype may be modulated by events that occurred during that critical period of life

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome

Study objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies

Neural control of fasting-induced torpor in mice

Torpor is a peculiar mammalian behaviour, characterized by the active reduction of metabolic rate, followed by a drop in body temperature. To enter torpor, the activation of all thermogenic organs that could potentially defend body temperature must be prevented. Most of these organs, such as the brown adipose tissue, are controlled by the key thermoregulatory region of the Raphe Pallidus (RPa). Currently, it is not known which brain areas mediate the entrance into torpor. To identify these areas, the expression of the early gene c-Fos at torpor onset was assessed in different brain regions in mice injected with a retrograde tracer (Cholera Toxin subunit b, CTb) into the RPa region. The results show a network of hypothalamic neurons that are specifically activated at torpor onset and a direct torpor-specific projection from the Dorsomedial Hypothalamus to the RPa that could putatively mediate the suppression of thermogenesis during torpor

Clinical implications of basic research; the role of orexin neurons in the central autonomic network.

Narcolepsy type 1 (NT1) and, to a lesser extent, neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, entail the loss of the hypothalamic neurons that release the hypocretin/orexin (H/O) neuropeptides. NT1 has been associated with autonomic anomalies including alterations in temperature regulation and cardiovascular control, particularly during sleep. A spectrum of autonomic dysfunctions also characterizes neurodegenerative diseases. The central autonomic network (CAN) is an interconnected set of brain structures that are critical for the control of autonomic preganglionic neurons. The H/O neurons include pre-autonomic neurons that directly target preganglionic sympathetic neurons in the intermediolateral column of the spinal cord and parasympathetic neurons in the dorsal motor nucleus of the vagus nerve. The H/O neurons also project to and modulate the activity of other CAN structures that include pre-autonomic neurons, such as the rostral ventromedial medulla and caudal raphe nuclei, the rostral ventrolateral medulla and the hypothalamic paraventricular nucleus. In addition, the H/O neurons project to and modulate the activity of neurons in the nucleus of the solitary tract in the medulla, which receives and relays visceral afferent information, and in higher order structures of the CAN, such as the dorsomedial nucleus of the hypothalamus and the extended amygdala. The H/O neurons should, therefore, be regarded as a key component of the CAN. Functional alterations of the CAN due to H/O neuron deficiency might contribute to autonomic anomalies in patients with neurodegenerative diseases and are likely to underlie autonomic anomalies in patients with NT1

Cost-effective Dynamic Structural Health Monitoring with a compact and autonomous wireless sensor system

Dynamic Structural Health Monitoring (D-SHM) in an attractive holistic approach to Non-Destructive Testing (NdT), based on the premise that damage influences the dynamic behaviour of a structure by altering its stiffness, mass or energy dissipation properties. At present, the fact that the dynamic behaviour of a structure is severely affected by a variety of additional boundary and environmental conditions confines D-SHM to industrial applications where repeatability or environmental conditioning reduce the complexity of the problem, or where the technical and economical implications of costly and time-consuming test campaigns are not an issue. In this work, the "Smartbrick" platform - an autonomous battery-operated wireless device purpose-built for environmental and structural monitoring - has been equipped with a vibration sensor that captures detailed acceleration data in response to natural occurrences such as small seismic or human-induced events. This enhancement makes the SmartBrick a D-SHM-ready platform with multi-year battery life, which allows a dramatic reduction in both equipment and installation costs, thus potentially expanding the practice of D-SHM to a considerably larger number of existing and new structures