After my Ph.D. (University of Neuchâtel) and postdoctoral research (Georgia State University, Atlanta, USA) on invertebrate sensory physiology, I joined the Research Unit on Schizophrenia directed by Professor Kim Do in 2001.
I have been engaged in investigating the consequences of a redox dysregulation, namely a deficit in GSH, on brain development and function. Results from these studies indicate that a redox dysregulation could contribute to the pathophysiology of schizophrenia. Indeed, a compromised GSH system affects brain regions (e.g. anterior cingulate cortex, ventral hippocampus), cell types (parvalbumin-expressing interneurons), coordinated neuronal network activity (high-frequency neuronal synchronization) and neurotransmission systems (NMDA receptors and dopamine receptor-mediated signalling) which are known to be abnormal in patients suffering from schizophrenia.
Together with my colleague Jan-Harry Cabungcal, we have also recently found that parvalbumin interneurons are particularly vulnerable to redox dysregulation during their maturation when the specialized extracellular matrix (called perineuronal nets), that enwraps these interneurons and protect them against oxidative stress, is not yet fully developed. Interestingly, the perineuronal nets are also strongly reduced in patients, thus underlying a vulnerability of parvalbumin interneurons to oxidative stress in schizophrenia.
- Extracellular and intracellular electrophysiological techniques to study synaptic function and plasticity, synchronized neuronal activity in brain slices
- Calcium-imaging and other time-lapse fluorescent measurements in primary cultures
- Biochemical and enzymatic methods to measure GSH system
- evelopment of electrophysiological methods for in-vivo recordings in behaving mice (électroencephalography, EEG)
- “Cellular and molecular mechanisms of synaptic plasticity”
- “Anomalies of interneurons and neuronal synchronization in psychiatric diseases”
- “Cholinergic system and therapeutic treatments available or in development against Alzheimer’s disease”
- Steullet P., Neijt H.C., Cuénod M., Do K.Q. (2006) Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia. Neuroscience 137: 807-819.
- Kovács K.A., Steullet P.*, Steinmann M., Do K.Q., Magistretti P.J., Halfon O., Cardinaux J.R. (2007) TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity. Proceedings of the National Academy of Sciences USA 104: 4700-4705.
- Steullet P., Lavoie S., Guidi R., Kraftzik R., Gysin R., Cuénod M., Do K.Q. (2008) A glutathione deficit alters dopamine modulation of L-type calcium channels via D2 and ryanodine receptors in neurons. Free Radical Biology & Medicine 44: 1042-1054.
- Steullet P., Cabungcal J.H., Kulak A., Kraftzik R, Chen Y., Dalton T.P., Cuénod M., Do Q.K (2010) Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations and Related Behaviors. Journal of Neuroscience 30: 2547-2558.
- Cabungcal J.H., Steullet P., Kraftsik R, Cuénod M., Do K.Q. (2013) Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine. Biological Psychiatry 73: 574-582.
- Cabungcal J.H., Steullet P.*, Morishita H., Kraftsik R., Cuénod M., Hensch T., Do K.Q. (2013) The perineuronal net protects fast-spiking interneurons against oxidative stress. Proceedings of the National Academy of Sciences USA) 110: 9130-9135.
- Steullet P., Cabungcal J.H., Kulak A., Cuénod M., Schenk F., Do Q.K. (2011) Glutathione deficit in animal models of schizophrenia. In: Animal Models of Schizophrenia and Related Disorders. Neuromethods 59 (Ed., P O’Donnell), Springer Science+Business Media, LLC 2011, pp. 149-188.
- Kulak A., Steullet P., Cabungcal J.H., Werge T., Ingason A., Cuénod M., Do Q.K. (2013) Redox dysregulation in the pathophysiology of schizophrenia and bipolar disorder: insights from animal models. Antioxidants and Redox signaling 18: 1428-1443.