European Sleep Research Laboratories

PRISM: Physiological Regulation in Sleeping Mice

University of Bologna
Department of Biomedical and Neuromotor Sciences - Physiology

PhD,MD
Giovanna Zoccoli
Piazza di Porta S. Donato, 2
40126 Bologna Italy


Position Associate Professor Phone +39 051 2091726 Fax +39 051 2091737 Contact E-Mail giovanna.zoccoli@unibo.it Website http://www.unibo.it/docenti/giovanna.zoccoli   Research Domain
  • Basic Animal

Keywords
  • Molecular Biology-Endocrinology-Biochemistry
  • Genetics of Sleep
  • Sleep and Body Functions (Cardio-Respiratory, Thermoregulation/Metabolism, Endocrine)
  • Sleep Physiology-Neurophysiology in Animal
  • Biological Rhythms

Laboratory Description Any given change in genetic information typically entails an array of differences in interacting physiologic functions, much as a beam of light may be dispersed in its component colours, Physiologic functions such as cardiovascular and respiratory control differ widely between wake-sleep behaviours. Mice are the mammalian species of choice for studies on functional genomics.

The PRISM lab investigates cardiorespiratory phenotype as a function of the wake-sleep behaviour in mice harbouring changes in genetic information, with a focus on genetically-engineered mouse models of human diseases. The main goal of this research is to help unravel the central neural and genetic mechanisms that underlie the physiologic and pathologic effects of sleep on cardiorespiratory control.

Research activity at the PRISM lab is presently focused on the study of hypothalamic integrative activity during sleep. The hypothalamus is a key region in the control of diverse physiologic functions, such as thermoregulation, osmoregulation, metabolism, and autonomic cardiovascular control. The hypothalamic networks underlying these functions are tightly entangled and share common substrates with the regulation of wake-sleep states. Mouse strains with genetic impairments of specific signalling molecules are a powerful tool to understand the role of specific neurotransmitters, neuromodulators, and neural pathways in integrative hypothalamic function during sleep.

The key technical asset of the PRISM lab is to perform simultaneous long-term recordings of multiple physiologic signals in freely-behaving mice. Blood pressure and heart rate are measured by telemetry, which is the technique at the state of the art in conscious mice. These measurements are synchronized with electroencephalographic and electromyographic (postural muscle tone) signals acquired with conventional cable transmission. Respiratory activity is monitored non-invasively with the technique of whole-body plethysmography, which is coupled to measurement of diaphragm electromyography to discriminate central from obstructive apnoeas. Stereotaxic implantation of intracerebral microcannulas allows selective pharmacological manipulation of hypothalamic circuitry. The PRISM lab is also equipped for development and maintenance of mouse colonies. Mouse genotyping with qualitative PCR, gene expression analysis with real-time quantitative PCR, and immunoenzymatic/immunofluorescent assays on plasma and tissue samples are performed with state-of-the-art molecular biology equipment in collaboration with the Centre for Applied Biomedical Research – CRBA at the Bologna University Hospital. Finally, researchers at the PRISM lab are actively involved in translating mathematic tools for analysis and modelling of biosignals developed in the lab to the clinical setting by means of collaborative studies on human subjects.

Technical Capabilities and areas of expertise EEG/EMG measurements in mice
Sleep deprivation (gentle handling) in mice
Sleep scoring and analysis in mice
Telemetric measurement of blood pressure and heart rate in mice
Measurement of respiratory function with whole-body plethysmography and diaphragmatic EMG in mice
Intra-cerebroventricular infusion in freely-behaving mice during wakefulness and sleep
Development and maintenance of colonies of genetically-engineered mice, mouse genotyping (PCR)
Gene expression analysis (qRT-PCR)
Immunoenzymatic/immunofluorescent assays
Advanced mathematic analysis and modelling of biosignals included spontaneous cardiovascular fluctuations
Software programming (SPSS, Matlab, Labview, Berkeley Madonna) for customized data acquisition and analysis

Additional Descriptors, Keywords Cardiorespiratory regulation and sleep
Central autonomic control during sleep
Functional genomics

Selected Publications in the 5 past years Articles in Peer Review Journals:

Silvani A., Bastianini S., Berteotti C., Franzini C., Lenzi P., Lo Martire V., Zoccoli G. Sleep modulates hypertension in leptin-deficient obese mice. Hypertension, 53: 251-255, 2009.

Silvani A., Bastianini S., Berteotti C., Franzini C., Lenzi P., Lo Martire V., Zoccoli G. Central and baroreflex control of heart period during the wake-sleep cycle in consomic rats with different genetic susceptibility to hypertension. Clin.Exp. Pharmacol. Physiol., 37:322-327, 2010.

Silvani A., Bastianini S., Berteotti C., Franzini C., Lenzi P., Lo Martire V., Zoccoli G. Dysregulation of heart rhythm during sleep in leptin-deficient obese mice. Sleep, 33:355-361, 2010.

Plazzi G., Moghadam K.K., Maggi L.S., Donadio V., Vetrugno R., Liguori R., Zoccoli G., Poli F., Pizza F., Pagotto U., Ferri R. Autonomic disturbances in narcolepsy, Sleep Med. Rev, 15: 187-196, 2011.

Bastianini S., Silvani A., Berteotti C., Elghozi, J.L., Franzini C., Lenzi P., Lo Martire V., Zoccoli G. Sleep-related changes in blood pressure in hypocretin-deficient narcoleptic mice. Sleep, 34: 213-218, 2011.

Bastianini S., Silvani A., Berteotti C., Lo Martire V., Zoccoli G. High-amplitude theta wave bursts during REM sleep and cataplexy-like state in hypocretin-deficient narcoleptic mice. J. Sleep Res. 21: 185-188, 2012.

Bastianini S., Silvani A., Berteotti C., Lo Martire V., Zoccoli G. Mice show circadian rhythms of blood pressure during each wake-sleep state. Chronobiol. Internat. 29: 82–86, 2012.

Silvani A., Bastianini S., Berteotti C., Lo Martire V., Zoccoli G. Control of cardiovascular variability during undisturbed wake-sleep behavior in hypocretin-deficient mice . Am J Physiol Regul Integr Comp Physiol., 302:R958-64, 2012.

Lo Martire V., Silvani A., Bastianini S., Berteotti C., Zoccoli G. Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons. PLoS One 7, e47032, doi: 10.1371/journal.pone.0047032. 2012.

Bastianini S., Crepaldi M., Demarchi D., Gabrielli A., Lolli M., Margotti A., Villani G., Zhang Z., Zoccoli G., A 0.18 μm CMOS Low-Power Radiation Sensor for Asynchronous Event-Driven UWB Wireless Transmission. Nucl. Instrum. Meth A, doi: 10.1016/j.nima.2013.05.008. 2013

Silvani A., Bastianini S., Berteotti C., Cenacchi G., Leone O., Lo Martire V., Papa V., Zoccoli G. Sleep and cardiovascular phenotype in middle-aged hypocretin deficient narcoleptic mice. J. Sleep Res. 2013, in press.

Bastianini S., Silvani A., Berteotti C., Lo Martire V., Zoccoli G. A critical role for hypocretins in pregnancy. J. Sleep Res. 2013, accepted.

Silvani A., Bastianini S., Berteotti C., Lo Martire V., Zoccoli G.Treating hypertension by targeting orexin receptors: potential effects on the sleep-related blood pressure dipping profile. J. Physiol., accepted.

Silvani A, Dampney RAL. Central control of cardiovascular function during sleep (Invited Review). Am. J. Physiol. Heart Circ. Physiol., accepted.

Grimaldi D, Silvani A, Benarroch E, Cortelli P. Orexin/hypocretin system and autonomic control: new insights and clinical correlations (Invited Review) Neurology, accepted.

Silvani A., Bastianini S., Berteotti C., Lo Martire V., Mazza R., Pagotto U., Quarta C., Zoccoli G. Multiple sleep derangements in mice lacking cannabinoid type 1 receptors. PLoS One, submitted.


Chapters in Multi-author Books:

Zoccoli G., Walker A.M. (2010) The circulation in sleep in early life; critical phases in its functional development and neural control. In: Vegetative Functions and Their Interactions in the Neonate. Chardon K (Ed), Research Signpost, Trivandrum, Kerala, India, pp 141-159.

Zoccoli G, Amici R, Silvani A. (2011) The hypothalamus and its functions. In: Narcolepsy. Pathophysiology, Diagnosis, and Treatment. Baumann CR, Bassetti CL and Scammell TE (eds). Springer, 1st Edition, pp 191-204.

Zoccoli G., Silvani A. and Franzini C. (2013) Sleep and the Peripheral Vascular System. In: Kushida C.A. (ed.) The Encyclopedia of Sleep, Vol. 1, pp. 563-567. Waltham, MA: Academic Press.


Key Publications of the Laboratory Zoccoli G., Walker A.M., Lenzi P., Franzini C. The Cerebral Circulation during Sleep: regulation mechanisms and functional implications. Sleep Med. Rev., 6: 443-455, 2002.

Franzini C. Cardiovascular Physiology: The Peripheral Circulation. In: Principles and Practice of Sleep Medicine. M.H. Kryger, T. Roth, W.C. Dement. (Eds), 4th Ed., Elsevier, Philadelphia, 2005, pp 203 - 212.

Silvani A, Lenzi P. Reflex Cardiovascular Control in Sleep. In: The Physiologic Nature of Sleep. Parmeggiani P.L., Velluti R.A. (Eds), Imperial College Press, London, 2005, pp. 351-369.

Zoccoli G., Bojic T., Franzini C. Regulation of Cerebral Circulation during Sleep. In: The Physiologic Nature of Sleep. Parmeggiani P.L., Velluti R.A. (Eds), Imperial College Press, London, 2005, pp. 351-369.

Silvani A. Physiological sleep-dependent changes in arterial blood pressure: central autonomic commands and baroreflex control (Invited Brief Review). Clin Exp Pharmacol Physiol, 35: 987-94, 2008.

Franzini C. Sleep and Blood Flow. In: Atlas of Clinical Sleep Medicine, M.H Kryger (Ed), Saunders Elsevier, Philadelphia, 2010, pp 49-53.

Zoccoli G., Walker A.M. The Circulation in Sleep in Early Life; critical phases in its functional development and neural control. In: Vegetative Functions and Their Interactions in the Neonate. Chardon K (Ed), Research Signpost, Trivandrum, Kerala, India, 2010, pp 141-159.

Plazzi G., Moghadam K.K., Maggi L.S., Donadio V., Vetrugno R., Liguori R., Zoccoli G., Poli F., Pizza F., Pagotto U., Ferri R. Autonomic disturbances in narcolepsy, Sleep Med. Rev, 15: 187-196, 2011.

Zoccoli G, Amici R, Silvani A. The hypothalamus and its functions. In: Narcolepsy. Pathophysiology, Diagnosis, and Treatment. Baumann CR, Bassetti CL and Scammell TE (eds). Springer, 1st Edition, 2011, pp 191-204.

Zoccoli G., Silvani A. and Franzini C. (2013) Sleep and the Peripheral Vascular System. In: Kushida C.A. (ed.) The Encyclopedia of Sleep, Vol. 1, pp. 563-567. Waltham, MA: Academic Press.

Silvani A, Dampney RAL. Central control of cardiovascular function during sleep (Invited Review). Am. J. Physiol. Heart Circ. Physiol., accepted.

Grimaldi D, Silvani A, Benarroch E, Cortelli P. Orexin/hypocretin system and autonomic control: new insights and clinical correlations (Invited Review) Neurology, accepted.

Current/Completed Grants (past 5 years) Completed Grants:
University of Bologna: Strategic Project 2006, RFO 2007, RFO 2008, RFO 2009, RFO 2010, RFO 2011.

Current Grants:
University of Bologna: RFO 2009, RFO 2010
Foundation Cassa di Risparmio Bologna: Role of hypothalamic neurogenesis in the development of obesity and its sleep and cardiovascular comorbidities.
Ministry of Instruction, University and Research, Italy: PRIN 2008: Role of hypocretinergic system in thermoregulatory cardiovascular control during wake and sleep; PRIN 2009: Wake-sleep and circadian mechanisms of the pathological changes in arterial blood pressure in animal models of diet-induced obesity.

 
Other laboratory Members
 
Title PhD,MD First Name Alessandro Last Name Silvani Position Assistant Professor E-Mail alessandro.silvani3@unibo.it  
Title PhD First Name Chiara Last Name Berteotti Position Assistant Professor E-Mail chiara.berteotti@unibo.it  
Title PhD First Name Stefano Last Name Bastianini Position Post-doc E-Mail stefano.bastianini3@unibo.it  
Title PhD First Name Viviana Last Name Lo Martire Position Post-doc E-Mail viviana.lomartire2@unibo.it  
Collaborations
 
Title PhD First Name Rosemary Last Name Horne Position Associate Professor Institution Monash University, Melbourne  
Title PhD First Name Gary Last Name Cohen Institution Karolinska Institute, Stockholm  
Title PhD,MD First Name Hiroshi Last Name Ohtsu Position Professor Institution Tohoku University, Sendai, Japan  
Title PhD,MD First Name Jian-Sheng Last Name Lin Position Professor Institution Université Claude Bernard, Lyon, France  
Title PhD First Name Roger Middle Name AL Last Name Dampney Position Professor Institution University of Sidney  
Title MD First Name Pietro Last Name Cortelli Position Associate Professor Institution Univerity of Bologna  
First Name Uberto Last Name Pagotto Position Assistant Professor Institution University of Bologna  
First Name Mauro Last Name Ursino Position Professor Institution University of Bologna  
Past Members
 
Title MD First Name Carlo Last Name Franzini Position Professor E-Mail carlo.franzini@unibo.it  
First Name Pierluigi Last Name Lenzi Position Professor E-Mail pierluigi.lenzi@unibo.it  
First Name Tullia Last Name Cianci Position Associate Professor E-Mail tullia.cianci@unibo.it  
Title PhD First Name Vera Last Name Ferrari E-Mail vera.ferrari@unibo.it