Neurobiology of Sleep Lab, University of Belgrade

Institute for Biological Res - Sinisa Stankovic

Contact:
Jasna Saponjic
Position:
Research Professor
Address:
Despot Stefan Blvd. 142
City:
Belgarde
Country:
Serbia
Phone:
+381 11 2078426
Fax:
+381 11 2761433
Research Domain
  • Basic Animal
Keywords
  • Neurological Sleep Disorders
  • Behavioural Sleep Disorders
  • Biological Rhythms
  • Sleep Physiology-Neurophysiology in Animal

Laboratory description

Our current research focuses on the neurobiology of sleep and sleep-related breathing in the animal models “in vivo” of healthy aging and neuropathology of the most common neurodegenerative diseases of elderly (Alzheimer’s Disease (AD), Parkinson’s Disease (PD), different types of dementia), aimed to give a new insight into understanding of normal and abnormal sleep, the mechanisms of sleep related behavioural disorders, particularly sleep apnea syndrome, and to identify the neural networks responsible for modifying the regulation of sleep and breathing pattern in different sleep/wake states.

Since underlying pathology of AD and PD involves the selective loss of specific neuronal population, an important role of the cholinergic system in their etiology, and the ascending pattern of neurodegeneration progression, from REM sleep-related brainstem regulatory structures to basal areas of the brain, in our research we use the rat models of unilateral or bilateral lesion of the nucleus basalis (NB; the main cortical cholinergic nucleus), and nucleus pedunculopontine tegmentum, (PPT; the main cholinergic nucleus of the brainstem – pons) as the experimental models of brain functionally distinct cholinergic neuropathology.

We follow the severity and progression of disorder caused by neurodegenerative process by electroencephalography (EEG) and electromyography (EMG): by the changes of sleep/wake states and NREM/REM cycling, EEG rhythms or EEG oscillations. We correlate all changes within EEG with the changes in breathing pattern using the methods of linear and nonlinear analysis to estimate the onset, progression, and severity of the disorder. We believe that EEG potentially presents a rich source of still unrevealed information related to functional, physiological, and pathological status of the brain. Developing the new methods for EEG processing and modelling will significantly contribute in understanding the mechanisms of sleep regulation, detection of disease related sleep and sleep-related breathing disorders, and in estimation of the neurodegenerative disease progression.

Complementary studies in the animal models of human neurodegenerative pathology will highly enrich the development of practical, sensitive and reliable methodology for early detection of the sleep behavioural disordered patients, who are at risk for developing Alzheimer’s and Parkinson’s Disease, or for the prevention and alteration of approaches for therapy.


Technical Capabilities and areas of expertise

– “in vivo” sleep recordings in animal models- stereotaxically guided microinfusions “in vivo” by using Digital Lab Standard Stereotaxic Instrument (Stoelting Co.) with a Hamilton syringe or with the multibarrel pipete pressure injections in nanoliter volumes.
– surgical procedure for the EEG and EMG electrodes implantations for chronic sleep recording in rats and mice using A-M System Inc. Model 3600, Carlborg, WA, USA for A/D conversion, amplification, and filtering and DataWave SciWorks Experimenter Version 8.0 (Datawave Technologies, Longmont, CO, USA) for recording.

– brain tissue processing and histochemistry

– sleep and EEG data analysis using the originally developed software using MATLAB 6.5.

– respiratory movements recordings in anesthetized rats using the piezo electric strain gauge (Infant-Ped Sleepmate Technologies, Midlothain, VA).

– respiratory pattern analysis in time domain by our originally developed Monotone Signal Segments Analysis for breath detection, differentiation, and the quantification of the eupnea, bradypnea/apnea and sigh breath-to-breath intervals within the respiratory pattern.


Selected Publications in the 5 past years:

Kesic S., Kalauzi A, Radulovacki M.,Carley D.W., Saponjic J. Coupling changes in cortical and pontine sigma and theta frequency oscillations following monoaminergic lesions in rat, Sleep and Breathing, 2011, 15(1), 35-47.

Spasic S., Kesic S., Kalauzi A., Saponjic J. Different anesthesia in rat induces distinct inter-structure brain dynamic detected by Higuchi fractal dimension, Fractals, 2011, 19(1), 113-123.

Spasic S., Kalauzi A., Kesic S., Obradovic M., Saponjic J. Surrogate data modeling the relationship between high frequency amplitudes and Highuchi fractal dimension of EEG signals in anesthetized rats, Journal of Theoretical Biology, 2011, 289, 160-166.

Spasic S., Nikolic Lj., Mutavdzic D, Saponjic J. Independent complexity patterns in single neuron activity induced by static magnetic field, Computer Methods and Programs in Biomedicine, 2011, 104(2), 212-218

Kalauzi A, Spasić S, Petrovic J, Ćiric J, Saponjic, J. Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat. Gen. Physiol. Bioph. 2012, 31, 163-171.

Bjelobaba I., Saponjic J. High volume microinfusion suppresses local astrocyte response within nucleus basalis of rat. Archives Italiennes de Biologie, 2013, 151, 24-32.

Saponjic J., Petrovic J., Kalauzi A., Ciric J., Lazic K., Radulovacki M., Carley D.W. Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder. Sleep & Biological Rhythms, 2013, 11, 105-115.

Petrovic J., Ciric J., Lazic K., Kalauzi A., Saponjic J. Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure. Experimental Neurology, 2013, 247, 562-571.

Petrovic J., Lazic K., Ciric J., Kalauzi A., Saponjic J. Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat. Behavioural Brain Research, 2013, 256, 108-118.

Petrovic J., Lazic K., Kalauzi A., Saponjic J. REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat. Behavioural Brain Research, 2014, 271, 258–268.

Bataveljic D., Petrovic J., Lazic K., Saponjic J., Andjus P. Glial response in the rat models of functionally distinct cholinergic neuronal denervations. Journal of Neuroscience Research, 2015, 93, 244-252.

Ciric J, Lazic K, Petrovic J, Kalauzi A, Saponjic J. Aging induced cortical drive alterations during sleep in rats. Mechanisms of Ageing and Development 2015, 146, 12-22.

Lazic K., Petrovic J., Ciric J., Kalauzi A., Saponjic J. Impact of anesthetic regimen on the respiratory pattern, EEG microstructure and sleep in the rat model of cholinergic Parkinson disease neuropathology, Neuroscience, 2015, 304, 1-13.


Key Publications of the Laboratory:

Saponjic J., Petrovic J., Kalauzi A., Ciric J., Lazic K., Radulovacki M., Carley D.W. Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder. Sleep & Biological Rhythms, 2013, 11, 105-115.

Petrovic J., Ciric J., Lazic K., Kalauzi A., Saponjic J. Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure. Experimental Neurology, 2013, 247, 562-571.

Petrovic J., Lazic K., Ciric J., Kalauzi A., Saponjic J. Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat. Behavioural Brain Research, 2013, 256, 108-118.

Petrovic J., Lazic K., Kalauzi A., Saponjic J. REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat. Behavioural Brain Research, 2014, 271, 258–268.

Ciric J, Lazic K, Petrovic J, Kalauzi A, Saponjic J. Aging induced cortical drive alterations during sleep in rats. Mechanisms of Ageing and Development 2015, 146, 12-22.

Lazic K., Petrovic J., Ciric J., Kalauzi A., Saponjic J. Impact of anesthetic regimen on the respiratory pattern, EEG microstructure and sleep in the rat model of cholinergic Parkinson disease neuropathology, Neuroscience, 2015, 304, 1-13.


Current/Completed Grants (past 5 years):

Project OI 173022 supported by Serbian Ministry of Science and Technological Development (2011-2015)

Project Title : NEUROBIOLOGY OF SLEEP IN AGING AND DISEASE – ELECTROENCEPHALOGRAPHIC MARKERS AND MODELING IN THE ESTIMATION OF DISORDER


Other laboratory Members

Title:  PhD

Name:  Jelena Petrovic

Position:  Postdoctoral Research Associate

Email:  jelenapetrovic@ibiss.bg.ac.rs

Title:  MSc

Name:  Vuk Milosevic

Position:  Postdoctoral Research Associate

Email:  vuk.milosevic@gmail.com

Title:  MSc

Name:  Jelena Ciric

Position:  Postdoctoral Research Associate

Email:  jelena.ciric@ibbis.bg.ac.rs

Name:  Nemanja Rajkovic

Position:  Postdoctoral Research Associate

Email:  nemanja.rajkovic@med.bg.ac.rs

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