Laboratory of Neurodegeneration and Experimental Therapy

Scientific profile

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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

Katarzyna Kuter-Nowak

Katarzyna Kuter-Nowak, dr hab.

Head

+48 12 6623226
room 3.36

Pracownicy zakładu

Elżbieta Lorenc-Koci, dr hab.

+48 12 6623272
room 338

Joanna Kula, dr

+48 12 6623286
room 337

Tomasz Lenda, mgr

+48 12 3343709
room 340

Agata Maziak, dr

+48 12 6623383
room 340

Emilija Napieralska, mgr

+48 12 3623286
room 3.37

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

Effect of 1,2,3,4,-tetrahydroisoquinoline administration under conditions of CYP2D inhibition on dopamine metabolism, level of tyrosine hydroxylase protein and the binding of [<sup>3</sup>H]GBR 12,935 to dopamine transporter in the rat nigrostriatal, dopaminergic system

Lorenc-Koci, E., Antkiewicz-Michaluk, L., Wardas, J., Zapała, M., Wierońska, J.

DOI: 10.1016/j.brainres.2004.02.044

Disposition of 1,2,3,4,-tetrahydroisoquinoline in the brain of male Wistar and Dark Agouti rats

Lorenc-Koci, E., Wójcikowski, J., Kot, M., Haduch, A., Boksa, J., Daniel, W.A.

DOI: 10.1016/j.brainres.2003.10.023

Contribution of the serotonin 5-HT<inf>1A</inf>receptor agonism of 8-OH-DPAT and EMD 128130 to the regulation of haloperidol-induced muscle rigidity in rats

Lorenc-Koci, E., Wardas, J., Bartoszyk, G.D., Wolfarth, S.

DOI: 10.1016/S0028-3908(03)00282-X

Influence of acute and chronic 1,2,3,4-tetrahydroisoquinoline administration on the expression of proenkephalin mRNA in the rat striatum

Wardas, J., Zapała, M., Lorenc-Koci, E.

DOI:

Decline in motor functions in aging is related to the loss of NMDA receptors

Ossowska, K., Wolfarth, S., Schulze, G., Wardas, J., Pietraszek, M., Lorenc-Koci, E., Mialowska, M., Coper, H.

DOI: 10.1016/S0006-8993(01)02601-4

Different action on dopamine catabolic pathways of two endogenous 1,2,3,4-tetrahydroisoquinolines with similar antidopaminergic properties

Antkiewicz-Michaluk, L., Michaluk, J., Mokrosz, M., Romanska, I., Lorenc-Koci, E., Ohta, S., Vetulani, J.

DOI: 10.1046/j.1471-4159.2001.00391.x

(S)-4C3HPG, a mixed group I mGlu receptor antagonist and a group II agonist, administered intrastriatally, counteracts parkinsonian-like muscle rigidity in rats

Lorenc-Koci, E., Wardas, J., Wolfarth, S., Pilc, A.

DOI: 10.1016/S0006-8993(01)02438-6

SCH 58261, an A <inf>2A</inf> adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats

Wardas, J., Konieczny, J., Lorenc-Koci, E.

DOI: 10.1002/syn.1070

Effect of acute administration of 1,2,3,4-tetrahydroisoquinoline on the levels of glutathione and reactive oxygen species, and on the enzymatic activity of γ-glutamyl transpeptidase in dopaminergic structures of rat brain

Lorenc-Koci, E., Soko, M.

DOI: 10.1016/S0306-4522(01)00421-3

The role of metabotropic glutamate receptor (mGluR) ligands in parkinsonian muscle rigidity

Wolfarth, S., Konieczny, J., Lorenc-Koci, E., Ossowska, K., Pilc, A.

DOI: 10.1007/s007260070038

Head

Katarzyna Kuter-Nowak, dr hab.

+48 12 6623226
room 3.36

See also