Matteo Cerri

University of Bologna | UNIBO · Department of Biomedical Science and Neuromotor Sciences DIBINEM

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular, projections from the preoptic area of the hypothalamus t...

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...

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...

Background: 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 cop...

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 suff...

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular projections from the preoptic area of the hypothalamus (P...

We recently described the first case of partial heterotopic liver transplantation replacing the spleen with delayed recipient hepatectomy to overcome the problem of organ shortage and to make possible debated indications for liver transplantation.1,2 The surgical technique of the RAVAS procedure was described in different steps: before planning the...

(Reprinted with permission from Br J Psychiatry 2005; 207: 235-242).

In mammals, torpor/hibernation is a state that is characterized by an active reduction in metabolic rate followed by a progressive decrease in body temperature. Torpor was successfully mimicked in non-hibernators by inhibiting the activity of neurons within the brainstem region of the Raphe Pallidus, or by activating the adenosine A1 receptors in t...

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-hibernat...

Each of the wake-sleep states is characterized by specific changes in autonomic activity and bodily functions. The goal of such changes is not always clear. During non-rapid eye movement (NREM) sleep, the autonomic outflow and the activity of the endocrine system, the respiratory system, the cardiovascular system, and the thermoregulatory system se...

Tau is a key protein in neurons, where it affects the dynamics of the microtubule system. The hyperphosphorylation of Tau (PP-Tau) commonly leads to the formation of neurofibrillary tangles, as it occurs in tauopathies, a group of neurodegenerative diseases, including Alzheimer's. Hypothermia-related accumulation of PP-Tau has been described in hib...

Physiological regulation can be defined as the integrated neural control mechanism underlying somatic, autonomic, and neuroendocrine activity. Such an integration occurs mostly at hypothalamic level. Physiological regulation is intrinsically heterogeneous between non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. During NREM sleep, i...

We thank the authors for their interest in our latest publication1,2. Liver transplantation (LT) for unresectable colorectal liver metastases (CRLM) has recently gained enthusiastic interest, as well as the RAPID technique proposed by Line et al3. RAPID and RAVAS techniques, although conceived to address unconventional indications for LT, are meant...

Under conditions of scarce food availability and cool ambient temperature, the mouse (Mus Musculus) enters into torpor, a state of transient metabolic suppression mediated in part by the autonomic nervous system. Hypothalamic orexins are involved in the coordination of behaviors and autonomic function. We tested whether orexins are necessary for th...

The notion of causal evidence in medicine has been the subject of wide philosophical debate in recent years. The notion of evidence has been discussed mostly in connection with Evidence Based Medicine and, more in general, with the assessment of causal nexus in medical, and especially research contexts. “Manipulative evidence” is one of the notions...

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15...

Imprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11-q13, is characterized by hypothalamic...

Rats are highly social animals that are able to emit audible sounds, but mainly intercommunicate in an ultrasonic interval of frequency (Brudzynski, ILAR journal, 2009). Adult rats emit ultrasonic vocalizations in two different frequencies, 22KHz and 50KHz. Vocalizations at 22KHz are mostly used in situations with negative connotations and are used...

Soon after the exit from a state of torpor/hibernation, a non‐REM sleep (NREMS) bout with high Delta electroencephalographic activity (EEG) power occurs, suggesting that the time passed in torpor/hibernation is a period of sleep deprivation (Deboer et al., J Comp Physiol A., 1994). The homeostatic nature of the after‐torpor Delta rebound has been c...

Torpor/hibernation is a survival strategy used by several mammals in periods of unfavorable environmental conditions, such as food shortage and low ambient temperature. It is characterized by an active reduction in metabolic rate followed by a decrease in body temperature. The decrease of metabolism and therefore in oxygen demand could be beneficia...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Il volume nasce dai convegni cassinati, di cui raccoglie i contributi più significativi che sono anche i temi “caldi” della ricerca in Neuroetica (il libero arbitrio, il rapporto body–mind, la coscienza, il neurodiritto, la neuroeconomy, l’intelligenza artificiale, ecc.), temi sui quali si focalizzano pure le domande che gli uomini si pongono in al...

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 therm...

Imprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11-q13, is characterised by hypothalamic...

The Raphe Pallidus (RPa) is a region of the brainstem that was shown to modulate the sympathetic outflow to many tissues and organs involved in thermoregulation and energy expenditure. In rodents, the pharmacological activation of RPa neurons was shown to increase the activity of the brown adipose tissue, heart rate, and expired CO2, whereas their...

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been prev...

Tau protein is of primary importance for many physiological processes in neurons, where it affects the dynamics of the microtubule system. When hyperphosphorylated (PP-Tau), Tau monomers detach from microtubules and tend to aggregate firstly in oligomers, and then in neurofibrillary tangles, as it occurs in a group of neurodegenerative disorders na...

A cellular degeneration of two thalamic nuclei belonging to the “limbic thalamus”, i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia. To better assess the physiological role of these nucle...

Manual scoring of polysomnography data is labor-intensive and time-consuming, and most existing software does not account for subjective differences and user variability. Therefore, we evaluated a supervised machine learning algorithm, SomnivoreTM, for automated wake–sleep stage classification. We designed an algorithm that extracts features from v...

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as "synthetic torpor" in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions,...

Despite substantial technical progress in the last decades, long-distance human space travel beyond the Earth-Moon system still represents a challenge. Resources for sustaining humans in good physical and mental health on such journeys are important drivers of complexity and cost. Every kilogram of mass and every cubic meter of volume reduction wil...

This review compares two states that lower energy expenditure: non-rapid eye movement (NREM) sleep and torpor. Knowledge on mechanisms common to these states, and particularly on the role of adenosine in NREM sleep, may ultimately open the possibility of inducing a synthetic torpor-like state in humans for medical applications and long-term space t...

St. Catherine of Siena suffered from an extreme form of holy fasting, a condition classified as anorexia mirabilis (also known as inedia prodigiosa). Historical and medical scholarships alike have drawn a comparison between this primaeval type of anorexia with a relatively common form of eating disorder among young women in the modern world, anorex...

While human hibernation would provide many advantages for medical applications and space exploration, the intrinsic risks of the procedure itself, as well as those involved if the procedure were to be misused, need to be assessed. Moreover, the distinctive brain state that is present during a hibernation-like state raises questions regarding the st...

Numerous data show a reciprocal interaction between REM sleep and thermoregulation. During REM sleep, the function of thermoregulation appears to be impaired; from the other hand, the tonic activation of thermogenesis, such as during cold exposure, suppresses REM sleep occurrence. Recently, both the central neural network controlling REM sleep and...

Therapeutic hypothermia is today used in several clinical settings, among them the gut related diseases that are influenced by ischemia/reperfusion injury. This perspective paved the way to the study of hibernation physiology, in natural hibernators, highlighting an unexpected importance of the gut microbial ecosystem in hibernation and torpor. In...

Obesity is known to be associated with alterations in wake-sleep (WS) architecture and cardiovascular parameters. This study was aimed at assessing the possible influence of diet-induced obesity (DIO) on sleep homeostasis and on the WS state‐dependent levels of arterial pressure (AP) and heart rate in the rat. Two groups of age-matched Sprague-Dawl...

Autonomic thermoregulation is a recently acquired function, as it appears for the first time in mammals and provides the brain with the ability to control energy expenditure. The importance of such control can easily be highlighted by the ability of a heterogeneous group of mammals to actively reduce metabolic rate and enter a condition of regulate...

In Fatal Familial Insomnia, sleep disruption and autonomic activation are concomitant with a marked cell loss in the Anteroventral (AV) and Mediodorsal (MD) thalamic nuclei (Lugaresiet al., Brain Pathol, 1998). This study was aimed at assessing, in the rat, the degree of cellular activation in AV and MD during the exposure to low ambient temperatur...

Hibernation is a state of reduced metabolic activity used by some animals to survive in harsh environmental conditions. The idea of exploiting hibernation for space exploration has been proposed many years ago, but in recent years it is becoming more realistic, thanks to the introduction of specific methods to induce hibernation-like conditions (sy...

Sleep is a complex behavior that cyclically alternates with wakefulness and is fundamental for both mental and physical wellness. During normal sleep the body acquires a specific posture; any active behavior is absent and mental activity typically oscillates between a state of “loss of consciousness” and the experience of dreaming. Sleep is, by its...

A major role in the wake-promoting effects of the activation of the lateral hypothalamus (LH) has been ascribed to a population of orexin (ORX)-containing neurons that send projections to central areas which regulate Wake-Sleep and autonomic function. Since, in the rat, a substantial amount of ORX neurons receive cholinergic projections from cells...

Background Interventions including physical exercise may help improve the outcomes of late-life major depression, but few studies are available.AimsTo investigate whether augmenting sertraline therapy with physical exercise leads to better outcomes of late-life major depression.Method Primary care patients (>65 years) with major depression were ran...

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 auton...

Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be...

Neural substrate of nausea is poorly understood, contrasting the wealth of knowledge about the emetic reflex. One of the reasons for this knowledge deficit is limited number and face validity of animal models of nausea. Our aim was to search for new physiological correlates of nausea in rats. Specifically, we addressed the question whether provocat...

Nausea is a prominent symptom and major cause of complaint for patients receiving anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is limited, and their efficacy is questionable. Currently, the development of new compounds with anti-nausea activity is hampered by the lack of physiological correlates of nausea. Physiological...

Thermoregulatory responses to temperature changes are not operant during REM sleep (REMS), but fully operant in non-REM sleep and wakefulness. The specificity of the relationship between REMS and the impairment of thermoregulation was tested by eliciting the reflex release of Thyrotropin Releasing Hormone (TRH), which is integrated at hypothalamic...

Somatic and autonomic physiological regulation varies during the ultradian sleep cycle in mammals. The basic somatic features of nonrapid eye movement (NREM) sleep are thermoregulatory posture, a decrease in antigravity muscle activity, and slow eye movements. The basic somatic features of rapid eye movement (REM) sleep are skeletal muscle atonia,...

Sleep restriction leads to metabolism dysregulation and to weight gain, which is apparently the consequence of an excessive caloric intake. On the other hand, obesity is associated with excessive daytime sleepiness in humans and promotes sleep in different rodent models of obesity. Since no consistent data on the wake-sleep (WS) pattern in diet-ind...

The possibility of inducing a suspended animation state similar to natural torpor would be greatly beneficial in medical science, since it would avoid the adverse consequence of the powerful autonomic activation evoked by external cooling. Previous attempts to systemically inhibit metabolism were successful in mice, but practically ineffective in n...

The effects of radiofrequency electromagnetic fields (RF-EMF) on the control of body energy balance in developing organisms have not been studied, despite the involvement of energy status in vital physiological functions. We examined the effects of chronic RF-EMF exposure (900 MHz, 1 V m−1) on the main functions involved in body energy homeostasis...

Wake-sleep (W-S) states are affected by thermoregulation. In particular, REM sleep (REMS) is reduced in homeotherms under a thermal load, due to an impairment of hypothalamic regulation of body temperature. The aim of this work was to assess whether osmoregulation, which is regulated at a hypothalamic level, but, unlike thermoregulation, is maintai...

Decrease in core temperature during torpor is concomitant with a left shift in the peak of the theta band of the EEG (5,5–9 Hz). It has been shown that inhibition of rostral ventromedial medulla (RVMM), produces a deep hypothermia in free behaving rats, caused by a massive peripheral vasodilation, and a concomitant inhibition of thermogenesis. The...

In different species, rapid eye movement sleep (REMS) is characterized by a thermoregulatory impairment. It has been postulated that this impairment depends on a general insufficiency in the hypothalamic integration of autonomic function. This study aims to test this hypothesis by assessing the hypothalamic regulation of body fluid osmolality durin...

Objectives: REM sleep (REMS) is characterized by the suspension of thermoregulation and by an instability of autonomic cardiovascular parameters such as arterial pressure (AP), heart rate (HR) and cutaneous vasomotion (1). Aim of this study was to investigate the relationship between cardiovascular regulation and thermoregulation during REM sleep b...

Objectives: A reciprocal relationship between disordered sleep and metabolic disturbances has been shown to develop in both humans and animals [1]. A recent study [2] carried out in mice fed a high-fat diet has shown that obesity is followed by an increase in the time spent in both NREM sleep (NREMS) and REM sleep (REMS). The present study was aime...

Putative sympathetic premotor neurons controlling cutaneous vasomotion are contained within the rostral ventromedial medulla (RVMM) between levels corresponding, rostrally, to the rostral portion of the nucleus of the facial nerve (RVMM(fn)) and, caudally, to the rostral pole of the inferior olive (RVMM(io)). Cutaneous vasoconstrictor premotor neur...

Thermoregulation is known to interfere with sleep, possibly due to a functional interaction at the level of the preoptic area (POA). Exposure to low ambient temperature (T(a)) induces sleep deprivation, which is followed by sleep rebound after a return to laboratory T(a). As two POA subregions, the ventrolateral preoptic nucleus (VLPO) and the medi...

Aim: Recent research proposes that putative sympathetic premotor neurons controlling cutaneous vasomotion are located within the rostral ventromedial medulla (RVMM), an area delimited rostrally by the nucleus of the facial nerve (RVMM(fn)) and caudally by the rostral pole of the inferior olive (RVMM(io)). Data from several experiments have shown t...

Studies conducted on anaesthetized animals have shown that neurons within the rostral ventromedial medulla (RVMM) can modulate the cardiac sympathetic outflow. Disinhibition of RVMM neurons by microinjection of the GABA-A antagonist bicuculline methiodide induces a strong increase in heart rate (HR), but inhibition of the same neurons by microinjec...

In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during...

Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24 degrees C. EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ran...

The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preopti...

Aim: Median Medullary Raphe (MMR) neurons are thought to be sympathetic premotor neurons controlling cutaneous vasomotion. Experiments designed to test this hypothesis have been so far performed in the animal under general anaesthesia. Aim of this study was to explore the role of RMM neurons in the free behaving animal. Methods: Male CD Sprague-...

Corticotropin releasing factor, acting at hypothalamic corticotropin releasing factor receptors, contributes to the neural signaling pathways mediating stress-related responses, as well as those involved in maintaining energy balance homeostasis. Sympathetically-regulated lipid metabolism and heat production in brown adipose tissue contributes to t...

Acute exposure to low ambient temperature modifies the wake-sleep cycle due to stage-dependent changes in the capacity to regulate body temperature. This study was carried out to make a systematic analysis of sleep parameters during the exposure to different low ambient temperatures and during the following recoveries at ambient temperature 24 degr...

A shift of physiological regulations from a homeostatic to a non-homeostatic modality characterizes the passage from non-NREM sleep (NREMS) to REM sleep (REMS). In the rat, an EEG index which allows the automatic scoring of transitions from NREMS to REMS has been proposed: the NREMS to REMS transition indicator value, NIV [J.H. Benington et al., Sl...

The lateral hypothalamic area, containing orexin neurons, is involved in several aspects of autonomic regulation, including thermoregulation and energy expenditure. To determine if activation of lateral hypothalamic area neurons influences sympathetically-regulated thermogenesis in brown adipose tissue, we microinjected bicuculline (120 pmol, 60 nl...

In the rat the exposure to an ambient temperature (Ta) of -10 degrees C induces an almost total REM sleep deprivation that results in a proportional rebound in the following recovery at normal laboratory Ta when the exposure lasts for 24 h, but in a rebound much lower than expected when the exposure lasts 48 h. The possibility that this may be rela...