Department of Physiology
Research at the Department of Physiology focuses on the effects of stress on the cerebral cortex and subcortical brain structures, such as hippocampus, hypothalamic paraventricular nucleus (PVN) and dorsal raphe nucleus. These brain areas are involved in the regulation of stress response, while chronic stress may adversely influence their function. It has been postulated that chronic stress exposure contributes to cognitive and psychiatric disorders and, possibly, neurodegenerative diseases, therefore studying the mechanisms associated with the effects of stress on brain function is one of the major issues in modern neurobiology.
Research using animal models, conducted in our laboratory, showed that repetitive exposure to stress increased an excitatory glutamatergic neurotransmission in the examined brain structures, except for the hippocampus. It has been also shown that these stress-induced alterations in synaptic plasticity are accompanied by changes in glucocorticoid (GR) and mineralocorticoid (MR) receptors as well as inducible nitric oxide synthase (iNOS) levels.
The 5-HT7 receptor, which has been identified recently, is a promising research target in neuropsychopharmacology because of its potential role in the etiology of psychiatric disorders. Our studies have shown that 5-HT7 receptor activation results in an increase in the excitability of hippocampal CA1 pyramidal neurons and chronic stress increases the 5-HT7 receptor reactivity. Moreover, administration of 5-HT7 receptor antagonists prevents stress-induced alterations in synaptic transmission and neuronal excitability in all examined brain structures. Similar effects were obtained following repeated administration of antidepressants.
The primary research method used in the Department of Physiology involve electrophysiological recordings from isolated rat and mouse brain specimens (sections). Other methods include the whole-cell patch-clamp recording technique, field-potential recordings in neuronal populations as well as in vitro electrophysiology of neurons and neuroglia. Moreover, the levels of prostaglandins, cytokines and stress-related hormones are measured using biochemical methods. Protein levels are measured using Western blot technique.
The most important recent discoveries
It has been shown that multiple (14 days) administration of 5-HT7 receptor antagonist SB 269970 (1.25 mg / kg) to rats abolished the impact of 5-HT7 receptor activation on CA1 and CA3 pyramidal neurons in rat hippocampal slices.
We have found that three-day immobility stress increased neurotransmission in the excitatory synapses located on parvocellular neurosecretory cells of the hypothalamic paraventricular nucleus (PVN). In contrast, GABAergic neurotransmission remained unchanged, while cell membranes excitability of the of the examined neurons was decreased.
Psychosocial Crowding Stress-Induced Changes in Synaptic Transmission and Glutamate Receptor Expression in the Rat Frontal Cortex.
Agnieszka Zelek-Molik, Bartosz Bobula, Anna Gądek-Michalska, Katarzyna Chorązka, Adam Bielawski, Justyna Kuśmierczyk, Marcin Siwiec, Michał Wilczkowski, Grzegorz Hess, Irena Nalepa
Biomolecules, 294 10.3390/biom11020294
Marcin Siwiec, Magdalena Kusek, Joanna Ewa Sowa, Krzysztof Tokarski, Grzegorz Hess
Neuropharmacology, S0028-3908(20)30316-6 10.1016/j.neuropharm.2020.108248
Astrocytes determine conditioned response to morphine via glucocorticoid receptor-dependent regulation of lactate release.
Urszula Skupio, Magdalena Tertil, Wiktor Bilecki, Justyna Barut, Michal Korostynski, Slawomir Golda, Lucja Kudla, Lucja Wiktorowska, Joanna E Sowa, Marcin Siwiec, Bartosz Bobula, Katarzyna Pels, Krzysztof Tokarski, Grzegorz Hess, Blazej Ruszczycki, Grzegorz Wilczynski, Ryszard Przewlocki
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 10.1038/s41386-019-0450-4
Tetrabromobisphenol A-induced depolarization of rat cerebellar granule cells: ex vivo and in vitro studies.
Dominik Diamandakis, Elzbieta Zieminska, Marcin Siwiec, Krzysztof Tokarski, Elzbieta Salinska, Jacek Lenart, Grzegorz Hess, Jerzy W Lazarewicz
Chemosphere, S0045-6535(19)30248-6 10.1016/j.chemosphere.2019.02.032
Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice.
Bartłomiej Pochwat, Bernadeta Szewczyk, Katarzyna Kotarska, Anna Rafało-Ulińska, Marcin Siwiec, Joanna E Sowa, Krzysztof Tokarski, Agata Siwek, Alexandre Bouron, Kristina Friedland, Gabriel Nowak
Frontiers in molecular neuroscience, 10.3389/fnmol.2018.00456
The 5-HT7 receptor antagonist SB 269970 ameliorates corticosterone-induced alterations in 5-HT7 receptor-mediated modulation of GABAergic transmission in the rat dorsal raphe nucleus.
Joanna Sowa, Magdalena Kusek, Marcin Siwiec, Joanna Ewa Sowa, Bartosz Bobula, Krzysztof Tokarski, Grzegorz Hess
Paulina Cieślik, Monika Woźniak, Katarzyna Kaczorowska, Piotr Brański, Grzegorz Burnat, Agnieszka Chocyk, Bartosz Bobula, Piotr Gruca, Ewa Litwa, Agnieszka Pałucha-Poniewiera, Agnieszka Wąsik, Andrzej Pilc, Joanna Wierońska
Frontiers in molecular neuroscience, 10.3389/fnmol.2018.00316
Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex.
Joanna Kula, Anna Gugula, Anna Blasiak, Bartosz Bobula, Joanna Danielewicz, Alan Kania, Grzegorz Tylko, Grzegorz Hess
Pflugers Archiv : European journal of physiology, 10.1007/s00424-017-2036-5
Nitric Oxide Synthase Inhibitor Attenuates the Effects of Repeated Restraint Stress on Synaptic Transmission in the Paraventricular Nucleus of the Rat Hypothalamus.
Magdalena Kusek, Anna Tokarska, Marcin Siwiec, Anna Gadek-Michalska, Bernadeta Szewczyk, Grzegorz Hess, Krzysztof Tokarski
Frontiers in cellular neuroscience, 10.3389/fncel.2017.00127
Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events.
Mariusz Popek, Bartosz Bobula, Joanna Sowa, Grzegorz Hess, Rafał Polowy, Robert Kuba Filipkowski, Małgorzata Frontczak-Baniewicz, Barbara Zabłocka, Jan Albrecht, Magdalena Zielińska
Molecular neurobiology, 10.1007/s12035-016-0367-4
Nucleus incertus Orexin2 receptors mediate alcohol seeking in rats.
Hanna E Kastman, Anna Blasiak, Leigh Walker, Marcin Siwiec, Elena V Krstew, Andrew L Gundlach, Andrew J Lawrence
Neuropharmacology, S0028-3908(16)30292-1 10.1016/j.neuropharm.2016.07.006
NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.
Magdalena Sikora, Krzysztof Tokarski, Bartosz Bobula, Joanna Zajdel, Kamila Jastrzębska, Przemysław Eligiusz Cieślak, Magdalena Zygmunt, Joanna Sowa, Magdalena Smutek, Katarzyna Kamińska, Krystyna Gołembiowska, David Engblom, Grzegorz Hess, Ryszard Przewlocki, Jan Rodriguez Parkitna
eNeuro, 10.1523/ENEURO.0084-15.2016 ENEURO.0084-15.2016
Excitatory orexinergic innervation of rat nucleus incertus - Implications for ascending arousal, motivation and feeding control.
Anna Blasiak, Marcin Siwiec, Agnieszka Grabowiecka, Tomasz Blasiak, Anna Czerw, Ewa Blasiak, Alan Kania, Zenon Rajfur, Marian H Lewandowski, Andrew L Gundlach
Neuropharmacology, 10.1016/j.neuropharm.2015.08.014 S0028-3908(15)30060-5
Prenatal stress enhances excitatory synaptic transmission and impairs long-term potentiation in the frontal cortex of adult offspring rats.
Joanna Sowa, Bartosz Bobula, Katarzyna Glombik, Joanna Slusarczyk, Agnieszka Basta-Kaim, Grzegorz Hess
PloS one, 10.1371/journal.pone.0119407
[Possible involvement of 5-HT₇ receptor in pathophysiology of affective disorders and action of antidepressant drugs].
Krzysztof Tokarski, Magdalena Kusek, Joanna Sowa, Bartosz Bobula
Postepy higieny i medycyny doswiadczalnej (Online),
- fluorescent microscopy
- G-protein coupled receptors
- glutamatergic receptors
- immobilization stress
- immune system
- ion channels
- long-term depression
- long-term potentiation
- neural circuit
- neural networks
- nitric oxide
- NMDA receptor
- serotonin receptors
- synaptic plasticity