Laboratory of Neurodegeneration and Experimental Therapy
Scientific profile
- About department
- Employees
Research profile
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by movement disorders (bradykinesia, muscle rigidity, resting tremor) and co-existing non-motor symptoms, including depression. The disease may be accompanied by action tremor. The pathomechanisms of this disease are poorly understood, the diagnosis is possible only in the late, irreversible stages, and the available symptomatic therapies are not effective and cause undesirable side effects.
Our research is focused on neurodegeneration of dopamine neurons, the development of compensatory processes, and mechanisms responsible for the major symptoms of PD and essential tremor. Another priority is the search for markers of different stages of PD and potential new drug targets.
We use animal models involving dopamine neuron (6-OHDA, MPP +, lactacystin, pesticides) and glial (fluorocitrate) cell damage, inhibition of their function (reserpine, tetrabenazine), dopamine receptors blockade (neuroleptics) or action tremor induction (harmaline). The course of degenerative processes and their consequences are analyzed at behavioral (disturbances of motility and coordination, tremor, catalepsy, depressive behavior), histological (immunohistochemistry, stereology), neurotransmitter (microdialysis, HPLC), receptor and transporter (autoradiography), molecular (proteomics and transcriptomics) and metabolic (mitochondrial activity, energy substrates evaluation) levels.
The above models are used to examine the mechanism affecting PD progression and find potential treatment targets and tools.
Research methods
- stereotaxic brain operations in rats and intracerebral administration of compounds
- behavioral methods:
– automatic measurement of locomotor activity, action tremor and other forms of rat motor behavior in actometers and tremorometers
– automatic measurement of asymmetric behavior in rats following unilateral damage of the dopamine system (rotameters)
– observation of rats’ behavior: catalepsy test (a model of akinesia, bradykinesia), measurement of tremulous jaw movements (a model of parkinsonian tremor), cylinder test (motor coordination test), dyskinesias
– running as a regular physical exercise training in automatic runways - histological methods: histological and immunohistochemical staining of brain sections, light and fluorecence microscopy, stereology, morphology anlysis, Sholl method
- biochemical methods: HPLC, brain microdialysis, autoradiography of receptors and transporters, measurement of energy substrates concentration in tissues and blood plasma
- molecular methods: Western blot, in situ hybridization, PCR, analysis of the mitochondrial respiratory complexes activity, 2-dimetional electrophoresis, DIGE
- computer imaging of brain sections, densitometry
The most important discoveries of the last 3 years
We have demonstrated that the dopamine system lesion in rats can model depression associated with Parkinson’s disease, and can be used to evaluate the efficacy and side effects of antidepressants as well as their interaction with L-DOPA.
It has been found, that changes in the protein complex composition and performance of the mitochondrial respiratory chain supercomplexes as well as the fluidity of mitochondrial membranes, observed following the dopamine system lesion in rats, might play an important role in the degenerative process and its compensation.
Retired Team Members
Prof. dr hab. Krystyna Ossowska – head of Department for many years
Prof. dr hab. Jadwiga Wardas
Pracownicy zakładu
Elżbieta Lorenc-Koci, dr hab.
Joanna Kula, dr
Tomasz Lenda, mgr
Agata Maziak, dr
Emilija Napieralska, mgr
Achievements
- Publications
- Grants
- Awards
Grant
grant NCN OPUS18 2019/35/B/NZ7/02862 Ćwiczenia fizyczne jako naturalny mechanizm indukujący neuroregenerację. Poszukiwanie nowych białek markerowych i celów terapeutycznych w chorobie Parkinsona
Katarzyna Kuter - Nowak, PhD
Grant
NCN grant, OPUS 14 [2018-08-03 do 2021-08-02] nr 2017/27/B/NZ7/00289 „Jak interakcja pomiędzy mikroglejem a astrocytami wpływa na funkcjonowanie neuronów w układzie dopaminergicznym. Analiza potencjalnego działania ochronnego substancji zmieniających fenotyp komórek glejowych" Wykonywany w IF PAN w Krakowie
Katarzyna Kuter - Nowak, PhD
Grant
Stypendium naukowe MOBILNOŚĆ PLUS, finansowane przez MNiSW. "Rola ochronna astrocytów w procesie degeneracji neuronów układu dopaminergicznego oraz w procesie funkcjonalnej kompensacji tego uszkodzenia. Badania funkcji i składu mitochondrialnych superkompleksów łańcucha oddechowego w zwierzęcych modelach wczesnej choroby Parkinsona"
Katarzyna Kuter - Nowak, PhD
Grant
Grant badawczy OPUS 3, nr 2012/05/B/NZ4/02599, finansowany przez NCN. „Rola astrocytów i metabolizmu komórkowego w procesie funkcjonalnej kompensacji uszkodzenia układu dopaminergicznego mózgu szczura. Analiza ekspresji AMPK i białek regulujących metabolizm energetyczny w kontekście choroby Parkinsona." Wykonywany w IF PAN w Krakowie.
Katarzyna Kuter - Nowak, PhD
Award
Zespołowa Nagroda Naukowa Wydziału V Nauk Medycznych PAN za cykl 3 publikacji pt. ”Rola astrocytów w mechanizmach kompensujących degenerację neuronów dopaminergicznych i w regulacji energetyki komórkowej układu czarno-prążkowiowego w zwierzęcym modelu wczesnej choroby Parkinsona”
Katarzyna Kuter - Nowak, PhD
Award
Nagroda Dyrektora IF PAN za publikacje o wysokim IF w 2018r.
Katarzyna Kuter - Nowak, PhD
The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5), Sildenafil, in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats
Elżbieta Lorenc-Koci, Kinga Kamińska, Tomasz Lenda, Jolanta Konieczny
DOI: 10.3390/molecules29184318
The effect of phencyclidine-mediated blockade of NMDA receptors in the early postnatal period on glutathione and sulfur amino acid levels in the rat brain as a potential causative factor of schizophrenia-like behavior in adulthood
Elżbieta Lorenc-Koci, Magdalena Górny, Grażyna Chwatko, Kinga Kamińska, Małgorzata Iciek, Zofia Rogóż
DOI: 10.1007/s43440-024-00607-3
Treatment with aripiprazole and N‐acetylcysteine affects anaerobic cysteine metabolism in the hippocampus and reverses schizophrenia‐like behavior in the neurodevelopmental rat model of schizophrenia
Magdalena Górny, Anna Bilska‐Wilkosz, Małgorzata Iciek, Zofia Rogóż, Elżbieta Lorenc‐Koci
DOI: 10.1111/febs.16944
N-Acetylcysteine and Aripiprazole Improve Social Behavior and Cognition and Modulate Brain BDNF Levels in a Rat Model of Schizophrenia
Zofia Rogóż, Kinga Kamińska, Marta Anna Lech, Elżbieta Lorenc-Koci
DOI: 10.3390/ijms23042125
Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague–Dawley Rats
Marta Anna Lech, Monika Leśkiewicz, Kinga Kamińska, Zofia Rogóż, Elżbieta Lorenc-Koci
DOI: 10.3390/ijms22126171
Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence
Danuta Kowalczyk-Pachel, Małgorzata Iciek, Anna Bilska-Wilkosz, Magdalena Górny, Joanna Jastrzębska, Kinga Kamińska, Paulina Dudzik, Małgorzata Filip, Elżbieta Lorenc-Koci
DOI: 10.3390/antiox10010074
Alterations in the Antioxidant Enzyme Activities in the Neurodevelopmental Rat Model of Schizophrenia Induced by Glutathione Deficiency during Early Postnatal Life
Magdalena Górny, Anna Bilska-Wilkosz, Małgorzata Iciek, Marta Hereta, Kinga Kamińska, Adrianna Kamińska, Grażyna Chwatko, Zofia Rogóż, Elżbieta Lorenc-Koci
DOI: 10.3390/antiox9060538
Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats
Magdalena Górny, Agnieszka Wnuk, Adrianna Kamińska, Kinga Kamińska, Grażyna Chwatko, Anna Bilska-Wilkosz, Malgorzata Iciek, Małgorzata Kajta, Zofia Rogóż, Elżbieta Lorenc-Koci
DOI: 10.3390/molecules24234253
Combined treatment with aripiprazole and antidepressants reversed some MK-801-induced schizophrenia-like symptoms in mice
Rogóż, Z., Wąsik, A., Lorenc-Koci, E.
DOI: 10.1016/j.pharep.2018.02.022
Interactions of the tricyclic antidepressant drug amitriptyline with L-DOPA in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Relevance to motor dysfunction in Parkinson's disease
Kamińska, K., Lenda, T., Konieczny, J., Wardas, J., Lorenc-Koci, E.
DOI: 10.1016/j.neuint.2018.10.004