Marco Luppi
Università di Bologna, Human and General Physiology, Faculty Member
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In different species, REM sleep (REMS) occurrence appears to be finely regulated on either a short (Vivaldi E, 1994) or a long-term basis (Parmeggiani PL, 1980). However, the hypothesis that REMS amount is homeostatically regulated is... more
In different species, REM sleep (REMS) occurrence appears to be finely regulated on either a short (Vivaldi E, 1994) or a long-term basis (Parmeggiani PL, 1980). However, the hypothesis that REMS amount is homeostatically regulated is challenged by data on humans which show that a scarce REMS rebound follows REMS deprivation (Horne J, 2000). Further analysis was carried out on data from an experiment in which 24 male Sprague-Dawley rats (250g) were exposed for 24h to different low ambient temperatures (Tas, ranging from \u201310\ub0C to 10\ub0C) and then allowed to recover for 4 days at normal laboratory Ta (Cerri M, 2005). REMS decreased proportionally with cold exposure, but a quick compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond an \u201calarm\u201d threshold (AT) corresponding to 22% of the REMS daily need. By using data from literature we have calculated that AT for cats (Parmeggiani PL, 1980) and humans (Endo T, 1998) should correspond to 72% and 234% of the REMS daily need. Examining the three species together, AT appears to increase proportionally to the average duration of the REMS episode. It also appears to be positively related to their brain mass (Kg) according to a power function: y = 226.03x 0.36 , r2=0.986. This would suggest that, in analogy to what has been observed regarding the body\u2019s energy needs, small mammals have a smaller capacity to buffer their REMS need than large ones
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Despite some difficulties in interpretation, results are also satisfactory with respect to the counting task, as testified by mean and median absolute error of, respectively, 0.8 and 1.
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Research Interests: Torpor and Homeostasis
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Research Interests: Osmoregulation and Wake
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BACKGROUND Music listening represents a gold standard in the evidence-based holistic nursing practice. However, music listening is seldom involved in orthopedic postoperative settings, and only a few related studies can be retrieved in... more
BACKGROUND Music listening represents a gold standard in the evidence-based holistic nursing practice. However, music listening is seldom involved in orthopedic postoperative settings, and only a few related studies can be retrieved in literature. PURPOSE The aim was to assess the effects of music during the orthopedic postoperative period, when patients frequently report pain and anxiety. METHOD A randomized controlled trial on 56 patients, equally divided in an experimental group treated with music and a control group in standard care, was conducted during their first-day of recovery from orthopedic surgery. The primary outcome was the pain level assessed with the VAS scale and the Short Form-McGill Pain Questionnaire. Secondary outcomes assessed were anxiety level, blood pressure, heart and respiratory rates and oxygen saturation. Following surgery, when clinically stabilized and soon after their return to their ward room, patients listened to music from a personal programmed pla...
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Homeothermy represents a remarkable step in animal evolution, albeit at a very high cost in terms of metabolic demand. The maintenance of core body temperature in mammals represents one of the prominent physiological components... more
Homeothermy represents a remarkable step in animal evolution, albeit at a very high cost in terms of metabolic demand. The maintenance of core body temperature in mammals represents one of the prominent physiological components contributing to the basal metabolic rate. Homeostatic thermoregulation is coordinated by the central nervous system by means of different strategies, spanning from behavioral modifications, aimed at finding a better environment, to the activation or inhibition of key regulatory mechanisms, which are mainly driven by the autonomic nervous system. The hypothalamic neuropeptide MCH plays a pivotal role in regulating basal metabolism, and the activation of this system results in a slowing down of the metabolic rate and also stimulates food intake. On the contrary, blocking the MCH system, in animal models, promotes a lean phenotype with higher body temperature. Even though MCH is not involved in thermoregulatory processes, modifying MCH activity induces metabolic rate modifications, and thermoregulation is modified accordingly. The activation of the MCH system also leads to the dampening of the normal daily oscillation of body temperature. The well-known involvement of MCH in wake-sleep cycle regulation, by stabilizing sleep, and in particular REM sleep, reinforces the hypothesis that the functions of metabolism, thermoregulation, and sleep regulation are closely linked.
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A role of VentroMedian Medullary Raphe (VMMR) neurons in cardiovascular (CV) control is suggested by studies on anaesthetized animals. VMMR neuron disinhibition increased heart rate, arterial pressure and sympathetic outflow to the heart... more
A role of VentroMedian Medullary Raphe (VMMR) neurons in cardiovascular (CV) control is suggested by studies on anaesthetized animals. VMMR neuron disinhibition increased heart rate, arterial pressure and sympathetic outflow to the heart (1). However, it is thought that VMMR neurons do not maintain the tonic sympathetic CV drive, due to the lack of major CV effects after VMMR inhibition (2). Since general anaesthesia affects sympathetic outflow and does not permit the measurement of heart rate variability (HRV), in the present study the role of VMMR neurons in CV control has been assessed in free behaving rats. Six male CD rats (Charles River), kept under a 12h:12h light-dark cycle at 24\ub10.5\ub0C ambient temperature were used. Under general anaesthesia (Diazepam, 5mg/Kg intramuscular; Ketamine-HCl, 100 mg/Kg, intraperitoneal), animals were implanted with electrodes for EEG and EKG recording, a thermistor to measure hypothalamic temperature (Thy), a microinjection guide cannula to target VMMR. One week after surgery, rats were randomly microinjected, on different days, with 100nl of the following: i) GABA-A agonist muscimol (1mM); ii) GABA-A antagonist bicuculline (1mM); iii) 0.9% saline. Preliminary analysis of data from muscimol injection was carried out during wake in two rats. HRV was analyzed within both the time (R-R mean; R-R standard deviation (STD-RR); root mean square successive difference (RMSSD)) and frequency domains (High (HF, 0.6\u20132.4 Hz) and Low Frequency (LF, 0.06\u20130.6 Hz) bands). Effects of injections were separated into six temporal blocks according to the dynamics of changes in core temperature following VMMR inhibition (3). At the end of the experiment, animals were sacrificed and histological control was carried out. Table 1 shows changes in HRV parameters and Thy (% of baseline levels, mean \ub1 SEM) during the six temporal blocks. The LF band, expression of CV sympathetic drive, was clearly reduced following VMMR neurons inhibition. Changes in HRV parameters appeared to be specifically due to VMMR neuron inhibition and not to changes in Thy. In conclusion, VMMR neurons seem to participate in maintaining tonic sympathetic CV outflow
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Introduction: Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During “synthetic torpor” (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of... more
Introduction: Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During “synthetic torpor” (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe Pallidus, a reversible brain Tau hyperphosphorylation occurs. The aim of the present study was to elucidate the – as yet unknown – molecular mechanisms underlying this process, at both a cellular and systemic level.Methods: Different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation were assessed by western blot in the parietal cortex and hippocampus of rats induced in ST, at either the hypothermic nadir or after the recovery of euthermia. Pro- and anti-apoptotic markers, as well as different systemic factors which are involved in natural torpor, were also assessed. Finally, the degree of microglia activation was determined through morphometry.Results: Overall, the results show that ST triggers a r...
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The hyperphosphorylation of tau protein (PPtau) in the brain is the main pathophysiological marker of tauopathies. Recently was found that when induced by a “synthetic torpor” (ST)1 condition (induced on rats), PPtau accumulations is... more
The hyperphosphorylation of tau protein (PPtau) in the brain is the main pathophysiological marker of tauopathies. Recently was found that when induced by a “synthetic torpor” (ST)1 condition (induced on rats), PPtau accumulations is reversible, as observed in hibernators2. Thus, ST uncover a latent physiological mechanism able to cope with PPtau and not specifically evolved with hibernation. Aim of the present work was to describe it.
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Abstract The interaction between a high-fat diet (HFD) and sleep regulation takes place against the common background of metabolism, at a hypothalamic level. Typical sleep modifications observed in laboratory rodents kept under an HFD... more
Abstract The interaction between a high-fat diet (HFD) and sleep regulation takes place against the common background of metabolism, at a hypothalamic level. Typical sleep modifications observed in laboratory rodents kept under an HFD regimen, compared to normal fed controls, are a lower daily amount of wakefulness mirrored by a higher amount of nonrandom eye movement (NREM) sleep that is also more fragmented and of a worse quality. REM sleep amount is mildly augmented in HFD-fed animals. The circadian distribution of the wake–sleep cycle is also modified and HFD also interferes with clock gene regulation. The opposite interaction is also true: prolonged sleep modifications may alter feeding behavior. These complex interactions involve different hypothalamic structures, but among these, the orexinergic system of the lateral hypothalamus may have a primary role. Animal models help to shed light on these processes, possibly suggesting more efficient approaches that can be considered in the treatment and prevention of obesity and metabolic syndromes.
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Research Interests: Neuroscience and Biology
Tau protein is of primary importance for neuronal homeostasis and when hyperphosphorylated (PP-Tau), it tends to aggregate in neurofibrillary tangles, as is the case with tauopathies, a class of neurodegenerative disorders. Reversible... more
Tau protein is of primary importance for neuronal homeostasis and when hyperphosphorylated (PP-Tau), it tends to aggregate in neurofibrillary tangles, as is the case with tauopathies, a class of neurodegenerative disorders. Reversible PP-Tau accumulation occurs in the brain of hibernating rodents and it was recently observed in rats (a non-hibernator) during synthetic torpor (ST), a pharmacological-induced torpor-like condition. To date, the expression of PP-Tau in the rat enteric nervous system (ENS) is still unknown. The present study immunohistochemically investigates the PP-Tau expression in the myenteric plexus of the ileum and colon of normothermic rats (CTRL) and during ST, focusing on the two major subclasses of enteric neurons, i.e., cholinergic and nitrergic.Results showed that both groups of rats expressed PP-Tau, with a significantly increased percentage of PP-Tau immunoreactive (IR) neurons in ST vs. CTRL. In all rats, the majority of PP-Tau-IR neurons were cholinergic....
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INDUCES A SUBSEQUENT INCREASE IN THE DURATION AND/OR IN THE INTENSITY OF SLEEP AND THAT the occurrence of sleep reduces sleep propensity. The outcome of the regulation of such a balance between sleep and wake has been addressed as “sleep... more
INDUCES A SUBSEQUENT INCREASE IN THE DURATION AND/OR IN THE INTENSITY OF SLEEP AND THAT the occurrence of sleep reduces sleep propensity. The outcome of the regulation of such a balance between sleep and wake has been addressed as “sleep homeostasis”.1,2 The major hindrance in a quantitative approach to sleep homeostasis lies in the fact that sleep consists of two different states, NREM sleep (NREMS) and REM sleep (REMS), which cyclically alternate on an ultradian basis. In particular: (1) it is not possible to carry out a selective NREMS deprivation without interfering with REMS occurrence; (2) selective REMS deprivation procedures have been shown to affect to some extent the quality of NREMS during deprivation3,4; (3) a complex interaction between NREMS and REMS rebounds has been observed following different sleep deprivation protocols5,6; and (4) NREMS and REMS regulation are influenced differently by circadian rhythmicity.7 In spite of this, many different “short-term” (minutes/...
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Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During “synthetic torpor” (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe... more
Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During “synthetic torpor” (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe Pallidus, a reversible brain Tau hyperphosphorylation occurs. The aim of the present study was to elucidate the – as yet unknown – molecular mechanisms underlying this process, at both a cellular and systemic level. Different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation were assessed by western blot in the parietal cortex and hippocampus of rats induced in ST, at either the hypothermic nadir or after the recovery of euthermia. Pro- and anti-apoptotic markers, as well as different systemic factors which are involved in natural torpor, were also assessed. Finally, the degree of microglia activation was determined through morphometry. Overall, the results show that ST triggers a regulated biochemical process w...
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Counting cells in fluorescent microscopy is a tedious, time-consuming task that researchers have to accomplish to assess the effects of different experimental conditions on biological structures of interest. Although such objects are... more
Counting cells in fluorescent microscopy is a tedious, time-consuming task that researchers have to accomplish to assess the effects of different experimental conditions on biological structures of interest. Although such objects are generally easy to identify, the process of manually annotating cells is sometimes subject to fatigue errors and suffers from arbitrariness due to the operator’s interpretation of the borderline cases. We propose a Deep Learning approach that exploits a fully-convolutional network in a binary segmentation fashion to localize the objects of interest. Counts are then retrieved as the number of detected items. Specifically, we introduce a Unet-like architecture, cell ResUnet (c-ResUnet), and compare its performance against 3 similar architectures. In addition, we evaluate through ablation studies the impact of two design choices, (i) artifacts oversampling and (ii) weight maps that penalize the errors on cells boundaries increasingly with overcrowding. In s...
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The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be... more
The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be effective in bringing core body temperature well below 30 °C in the rat, a non-hibernator: the first, based on the inhibition of a key relay in the central thermoregulatory pathway, the other, based on the activation of central adenosine A1 receptors. Although the role of mitochondria in the activation and maintenance of torpor has been extensively studied, no data are available for centrally induced hypothermia in non-hibernators. Thus, in the present work the respiration rate of mitochondria in the liver and in the kidney of rats following the aforementioned hypothermia-inducing treatments was studied. Moreover, to have an internal control, the same parameters were assessed in a well-consolidated model, i.e., mice during fasting-induced torpor. Our results show that state 3 respiration rate, which significantly decreased in the liver of mice, was unchanged in rats. An increase of state 4 respiration rate was observed in both species, although it was not statistically significant in rats under central adenosine stimulation. Also, a significant decrease of the respiratory control ratio was detected in both species. Finally, no effects were detected in kidney mitochondria in both species. Overall, in these hypothermic conditions liver mitochondria of rats remained active and apparently ready to be re-activated to produce energy and warm up the cells. These findings can be interpreted as encouraging in view of the finalization of a translational approach to humans.
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Research Interests: Psychology, Electroencephalography, Medicine, Biological Sciences, Fourier Analysis, and 15 moreCerebral Cortex, Hypothalamus, Animals, Male, Sleep, Body Size, Body temperature regulation, Exposure, Rats, Homeostasis, Rat, Cold, Motor activity, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood... more
Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the ...
