Professor Janusz Lipski

MD, PhD, DrSci

Biography

Professional and academic experience

Current appointment (from 1987): Chair in Neurophysiology, Deptartment of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

2007-present Foreign Member of the Polish Academy of Science (PAU, Krakow)
1987-present Professor of Neurophysiology, The University of Auckland, New Zealand
1984-87 Senior Research Fellow, Experimental Neurology Unit, The John Curtin School of Medical Research, ANU, Canberra, Australia
1980-84 Associate Professor (Dozent Dr.), Dept. of Physiology, Univ. of Warsaw, Poland
1977-79 UNESCO / IBRO Fellow, Dept. of Neurophysiology, Univ. of Goteborg, Sweden
1975-77 Lecturer and Senior Lecturer, Dept. of Physiology, Univ. of Warsaw, Poland

 

Research | Current

Research interests

  • Brain control of movement
  • Mechanisms of neurodegeneration and neuroprotection in neurological disorders
  • Pathophysiology of midbrain dopaminergic neurons and models of Parkinson's disease
  • Mechanisms of therapeutic action of L-DOPA (Levodopa) 
  • ADHD (Attention-deficit hyperactivity disorder)
  • Brain ischemia (hippocampus) and stroke models
  • Motoneurons and ALS (Motoneuron disease)
  • Electophysiology (incl. patch-clamp recording)
  • Electrochemistry
  • Optogenetics
  • Neuropharmacology
  • Immunocytochemistry and nerve cell imaging
  • Neurotoxicity (incl. excitotoxicity)
  • Calcium (incl. fura-2 imaging)
  • Oxidative stress and antioxidants
  • TRP channels
  • [Till 2002: Brain control of blood pressure and respiration]

 

Summary of current research programme

A key focus of my research is to understand the fundamental mechanisms which lead to Parkinson’s disease (PD), and to improve the current treatment of this disease. PD is a highly debilitating brain disorder which severely affects patients’ ability to move and causes tremor in the hands, stiff and painful muscles, frequents falls and slurred speech. Currently this disease affects ~11,000 New Zealanders, mainly those 60 years and above, and it is predicted that the number will double over a 25-year period as the population ages. It is caused by progressive loss of dopamine-producing neurons in the brain, and the most widely prescribed treatment relies on levodopa, a drug which increases dopamine release mainly by surviving neurons. However, after prolonged use the beneficial effects of levodopa gradually lessen and serious side effects develop known as dyskinesia.

We are investigating basic properties and pathophysiology of dopamine-producing nerve cells in the part of the brain called the Substantia Nigra, known to degenerate in PD, and studying the effects of neurotoxins (6-hydroxydopamine, rotenone, MPTP) and various drugs (incl. L-DOPA; levodopa) on these cells. The long term goal is to improve the existing treatment of PD by increasing the effectiveness of levodopa in dopamine production in PD patients, and to develop new medications based on improved knowledge of the properties of affected nerve cells.

Major experimental techniques which we use include electrophysiology (whole-cell patch-clamp and intracellular recording with sharp microelectrodes) both in vivo and in vitro, electrochemical detection of dopamine, optogenetics, calcium imaging, and pharmacological modulation of specific membrane receptors. Recently, we have developed a transgenic rat model in which the function of the dopamine transporter (DAT) is eliminated (DAT-KO rat). This model will allow us to investigate the mechanisms through which dopamine levels are controlled in the brain in the absence of confounding effects of DAT.

 

Recent publications (selected)

Yee AG, Forbes B, Cheung P-Y, Martini A, Burrell MH, Freestone PS & Lipski J. ‘Action potential and calcium dependence of tonic somatodendritic dopamine release in the Substantia Nigra pars compacta’. J. Neurochemistry. 2018. In press.

Karunasinghe RN, Dean JM & Lipski J. ‘Acute sensitivity of astrocytes in the Substantia Nigra to oxygen and glucose deprivation (OGD) compared to hippocampal astrocytes in brain slices’. Neuroscience Lett, 2018, doi.org/10.1016/j.neulet.2018.08.033.

Yee AG, Freestone PS, Bai JZ & Lipski, J. ‘Paradoxical lower sensitivity of Locus Coeruleus than Substantia Nigra pars compacta neurons to acute actions of rotenone. Experimental Neurology, 2017, 287: 34-43.

Karunasinghe RN, Grey AC, Telang R, Vlajkovic SM & Lipski J. ‘Differential spread of anoxic depolarization contributes to the pattern of acute neuronal injury after oxygen and glucose deprivation (OGD) in the Substantia Nigra in brain slice’. Neuroscience. 2017, 340: 359-372.

Burrell MH, Atcherley CW, Heien ML & Lipski J, ‘A novel electrochemical approach for prolonged measurement of absolute levels of extracellular dopamine in brain slices’. ACS Chem Neurosci, 2016, 6: 144-51.

Freestone PS, Wu XH, de Guzman G & Lipski J. ’Excitatory drive from the subthalamic nucleus attenuates GABAergic transmission in the Substantia Nigra pars compacta via endocannabinoids’. European J Pharmacol. 2015, 767: 144-151.

Yee A., Lee SM, Hunter MR, Glass M, Freestone PS & Lipski J. ‘Effects of the parkinsonian toxin MPP+ on electrophysiological properties of nigral dopaminergic neurons’. Neurotoxicology, 2015, 45: 1-11.

Freestone PS, Guatteo E, Piscitelli F, di Marzo V, Lipski J & Mercuri NB. ‘Glutamate spillover drives endocannabinoid production and inhibits GABAergic transmission in the Substantia Nigra pars compacta’. Neuropharmacology, 2014, 79:467-75.

Bai JZ & Lipski J. ‘Involvement of TRPV4 channels in Aβ(40)-induced cell death and astrocytic Ca(2+) signalling’. Neurotoxicology, 2013, 41: 64-72.

Guatteo E, Yee A, McKearney J, Cucchiaroni M L, Armogida M, Berretta N, Mercuri NB & Lipski, J. Dual effects of l-DOPA on nigral dopaminergic neurons. Exp Neurol., 2013, 247: 582-594.

Karunasinghe RN & Lipski J. ‘Oxygen and glucose deprivation (OGD)-induced spreading depression in the Substantia Nigra’. Brain Research, 2012. 1527: 209-221.

Chung KK, Freestone PS & Lipski J, ‘Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat’. J Neurophysiol, 2011, 106: 2865-2875.

Lipski J, Nistico R, Berretta N, Guatteo E, Bernardi G & Mercuri NB. ‘L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease?’ Prog Neurobiol, 2011, 9: 389-407.

Cucchiaroni ML, Freestone PS, Berretta N, Viscomi MT, Bisicchia,E, Okano H, Molinar M, Lipski J, Mercuri NB & Guatteo E. ‘Properties of dopaminergic neurons in organotypic mesencephalic-striatal co-cultures - evidence for a facilitatory effect of dopamine on the glutamatergic input mediated by α-1 adrenergic receptors’. European Journal of Neuroscience, 2011, 33: 1622-1636.

Yoon JJ, Green CR, Bai JZ, Lipski J & Nicholson LF. 'Effect of low Mg(2+) and bicuculline on cell survival in slice cultures'. International Journal of Neuroscience, 2010. 120, 752-759.

Bai JZ & Lipski J. ‘Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture’. Neurotoxicology, 2010, 31: 204-214.

Freestone PS, Chung KKH, Guatteo E, Mercuri B, Nicholson LFB & Lipski J. 'Acute action of rotenone on nigral dopaminergic neurons - involvement of reactive oxygen species and disruption of Ca2+ homeostasis', Euopean Journal of Neuroscienece, 2010, 30: 1849-1859.

Oswald MJ, Oorschot DE, Schulz JM, Lipski J & Reynolds JNJ. 'I-H current generates the afterhyperpolarisation following activation of subthreshold cortical synaptic inputs to striatal cholinergic interneurons', J. Physiol.(Lond.), 2009, 5875: 879-5897.

 

Selected publications and creative works (Research Outputs)