PRISM: Physiological Regulation in Sleeping Mice, University of Bologna

Department of Biomedical and Neuromotor Sciences - Physiology

Contact:
Giovanna Zoccoli
Position:
Associate Professor
Address:
Piazza di Porta S. Donato, 2, 40126
City:
Bologna
Country:
Italy
Phone:
+39 051 2091726
Fax:
+39 051 2091737
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

Name:  Alessandro Silvani

Position:  Assistant Professor

Email:  alessandro.silvani3@unibo.it

Title:  PhD

Name:  Chiara Berteotti

Position:  Assistant Professor

Email:  chiara.berteotti@unibo.it

Title:  PhD

Name:  Stefano Bastianini

Position:  Post-doc

Email:  stefano.bastianini3@unibo.it

Title:  PhD

Name:  Viviana Lo Martire

Position:  Post-doc

Email:  viviana.lomartire2@unibo.it


Collaborations

Title:  PhD

Name:  Rosemary Horne

Position:  Associate Professor

Institution:  Monash University, Melbourne

Title:  PhD

Name:  Gary Cohen

Institution:  Karolinska Institute, Stockholm

Title:  PhD MD

Name:  Hiroshi Ohtsu

Position:  Professor

Institution:  Tohoku University, Sendai, Japan

Title:  PhD MD

Name:  Jian-Sheng Lin

Position:  Professor

Institution:  Université Claude Bernard, Lyon, France

Title:  PhD

Name:  Roger AL Dampney

Position:  Professor

Institution:  University of Sidney

Title:  MD

Name:  Pietro Cortelli

Position:  Associate Professor

Institution:  Univerity of Bologna

Name:  Uberto Pagotto

Position:  Assistant Professor

Institution:  University of Bologna

Name:  Mauro Ursino

Position:  Professor

Institution:  University of Bologna


Past Members

Title:  MD

Name:  Carlo Franzini

Position:  Professor

Email:  carlo.franzini@unibo.it

Name:  Pierluigi Lenzi

Position:  Professor

Email:  pierluigi.lenzi@unibo.it

Name:  Tullia Cianci

Position:  Associate Professor

Email:  tullia.cianci@unibo.it

Title:  PhD

Name:  Vera Ferrari

Email:  vera.ferrari@unibo.it

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