Laboratory of Preclinical Studies in Neurodegenerative Diseases

Head: Grażyna NIEWIADOMSKA

Staff: Anna Gąsiorowska, Marcin Mazurkiewicz, Marcelina Góras, Teresa Cymbalak, Ewelina Kawka (PhD student)

Research profile:

Neurodegeneration is a common theme of many nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease, ALS, head trauma, epilepsy and stroke. The incidence of these devastating disorders is increasing rapidly in ageing population and current treatments are inadequate.
Our main research interest is to understand mechanisms involved in neural ageing. Towards this end, we have tried to implement new experimental protocols and conduct longitudinal studies that can be used in Alzheimer research and other neurodegenerative disorders. The work uses rats and transgenic mice and has centred on studies of the reversal of brain dysfunction induced by aging. We attempt to link cellular and behavioral levels of the brain processes present during physiological and pathological ageing. Currently the team’s main interest is development of novel treatments, animal models and diagnostic procedures for the nervous system diseases and assessment of toxicology, safety pharmacology, pharmacokinetics and complex behavioral effects of therapeutic compounds.

Methods:

1. microsurgery on the brain
2. histological and neuroanatomical examination
3. computational image analysis
4. behavioral examination
5. immunological staining: immunohistochemistry, immunocytology, Western blotting, ELISA
6. biochemical methods
7. preclinical study in toxicity, CNS, cardiovascular and respiratory safety pharmacology, histopathology, and diagnostics.

Current research activities:

- cholinergic anabolism and signalling,
- the retrograde transport of fluorescent NGF in basal forebrain cholinergic neurones and correlation of these changes with age-dependent structural reorganisation of the axonal cytoskeleton,
- pre-synaptic TrkA receptor expression and NGF-TrkA signalling,
- cytoskeletal transport and post-translational modifications of microtubule associated proteins during physiological ageing and neurodegenerative diseases in rat model systems,
- profiling age-related cognitive impairments in spatial memory tasks
- development of novel treatments for neurodegenerative diseases: testing in animal models and assessment of drug safety and pharmacology.

Selected publications:

Mietelska-Porowska A, Wasik U, Goras M, Filipek A, Niewiadomska G. Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci. 15(3): 4671-4713, 2014.

U. Wasik, G. Schneider, A. Mietelska-Porowska, M. Mazurkiewicz, H. Fabczak, S. Weis, C. Zabke , C.R. Harrington, A. Filipek, G. Niewiadomska. Calcyclin binding protein and Siah-1 interacting protein in Alzheimer’s disease pathology: neuronal localization and possible function. Neurobiology of Aging, 34: 1380-1388, 2013.

Kiryk A, Pluta R, Figiel I, Mikosz M, Ulamek M, Niewiadomska G, Jablonski M, Kaczmarek L, Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury. Behav Brain Res. 219 (1): 1-7, 2011.

G. Niewiadomska, A. Mietelska-Porowska, M. Mazurkiewicz. The cholinergic system, nerve growth factor and the cytoskeleton. Behav Brain Res 221(2):515-526, 2011.

Niewiadomska G., Baksalerska-Pazera M., Riedel G.: The septo-hippocampal system, learning and recovery of function, Progress in Neuropsychopharmacology & Biological Psychiatry 33:791-805 2009.