Department of Neuropsychopharmacology

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


Head

Katarzyna Kuter - Nowak, PhD

Phone number: +48 12 6623226
E-mail: kuter@if-pan.krakow.pl

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