Giovanna Zoccoli

Aim of the reserch activity performed in the laboratory "PRISM: Physiological Regulation in Sleeping Mice" at Department of Biomedical and Neuromotor Sciences (DIBINEM), Physiology Unit, is the study of regulatory processes  during the different states of wake-sleep cycle in genetically engenered mice.
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

Keywords
Cardiorespiratory regulation and sleep
Central autonomic control during sleep
Functional genomics

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

Berteotti C., Asti V., Ferrari V., Franzini C, Lenzi P., Zoccoli G., Silvani A. Central and baroreflex control of heart period during the wake-sleep cycle in spontaneously hypertensive rats. Am J Physiol (Regul Integr Comp Physiol.), 293: 293-298, 2007. IF 2010: 3,284

Berteotti C., Franzini C., Lenzi P., Zoccoli G., Silvani A. Surges of arterial pressure during rapid-eye-movement sleep in spontaneously hypertensive rats. Sleep, 31: 111-117, 2008. IF 2010: 5,486

Berteotti C., Franzini C, Lenzi P., Magosso E., Ursino M., Zoccoli G., Silvani A. The baroreflex contribution to spontaneous heart rhythm assessed with a mathematical model in rats. Autonom. Neurosci.: Basic and Clinical, 138: 24-30, 2008. IF 2010: 1,671

Silvani A., Grimaldi D., Vandi S., Barletta G., Vetrugno R., Provini F., Pierangeli G., Berteotti C., Montagna P., Zoccoli G., Cortelli P. Sleep-dependent changes in the coupling between heart period and blood pressure in human subjects. Am J Physiol (Regul Integr Comp Physiol.), 294: R1686-92, 2008. IF 2010: 3,284.

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. IF 2010: 1,960.

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. IF 2010: 6,908

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. IF 2010: 1,960

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. IF 2010: 5,486

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. IF 2010: 6.338

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. IF 2010: 5,486

Silvani A, Magosso E, Bastianini S, Lenzi P, Ursino M. Mathematical modeling of cardiovascular coupling: central autonomic commands and baroreflex control Autonom Neurosci: Basic and Clinical,162: 66-71, 2011 IF 2010: 1,671

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. IF 2010: 3,361

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. IF 2010: 5,576 

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. IF 2010: 3,284.

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, PLoS One 7, e47032, doi: 10.1371/journal.pone.0047032

Chapters in Multi-author Books:

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.

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, Franzini C. Sleep and the peripheral vascular system. In: Encyclopedia of Sleep. Kushida C et al. (eds), Elsevier, in 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, Franzini C. Sleep and the peripheral vascular system. In: Encyclopedia of sleep. Kushida C et al. (eds), Elsevier, Philadelphia, in press.