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 effects of cocaine on different redox forms of cysteine and homocysteine, and on labile, reduced sulfur in the rat plasma following active versus passive drug injections
Kowalczyk-Pachel, D., Chwatko, G., Iciek, M., Czyzyk, J., Filip, M., Włodek, L., Lorenc-Koci, E.
DOI: 10.1007/s12640-013-9403-6
Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA
Lorenc-Koci, E., Czarnecka, A., Lenda, T., Kamińska, K., Konieczny, J.
DOI: 10.1016/j.neuint.2013.09.021
The effect of lipoic acid on cyanate toxicity in different structures of the rat brain
Sokołowska, M., Lorenc-Koci, E., Bilska, A., Iciek, M.
DOI: 10.1007/s12640-013-9395-2
The extent of neurodegeneration and neuroprotection in two chemical in vitro models related to parkinson's disease is critically dependent on cell culture conditions
Jantas, D., Roman, A., Kuśmierczyk, J., Lorenc-Koci, E., Konieczny, J., Lenda, T., Lasoń, W.
DOI: 10.1007/s12640-012-9374-z
Two faces of 1,2,3,4-tetrahydroisoquinoline mode of action in the mammalian brain: Is it an endogenous neurotoxin or a neuromodulator?
Lorenc-Koci, E.
DOI: 10.1007/978-1-4614-1542-8_1
Different effects of intranigral and intrastriatal administration of the proteasome inhibitor lactacystin on typical neurochemical and histological markers of Parkinson's disease in rats
Lorenc-Koci, E., Lenda, T., Antkiewicz-Michaluk, L., Wardas, J., Domin, H., Śmiałowska, M., Konieczny, J.
DOI: 10.1016/j.neuint.2011.03.013
Neuroprotective effects of MAPK/ERK1/2 and calpain inhibitors on lactacystin-induced cell damage in primary cortical neurons
Jantas, D., Lorenc-Koci, E., Kubera, M., Lason, W.
DOI: 10.1016/j.neuro.2011.05.013
The effect of the uremic toxin cyanate (CNO<sup>-</sup>) on anaerobic cysteine metabolism and oxidative processes in the rat liver: A protective effect of lipoate
Sokołowska, M., Niedzielska, E., Iciek, M., Bilska, A., Lorenc-Koci, E., Włodek, L.
DOI: 10.3109/15376516.2011.556155
The effect of uremic toxin cyanate (OCN <sup>-</sup>) on anaerobic sulfur metabolism and prooxidative processes in the rat kidney: A protective role of lipoate
Iciek, M., Bilska, A., Lorenc-Koci, E., Włodek, L.B., Sokołowska, M.M.
DOI: 10.1177/0960327110394225