Dr. Grzegorz M. Wilczyński, Dr. Marcin Rylski, Dr. Filip A. Konopacki, Piotr Michaluk M.Sc., Dr. Paweł Okulski, Renata Amborska M.Sc., Dr. Jacek Jaworski, Dr. Joanna Dzwonek, Maciej Gawlak M.Sc.; led by Prof. Leszek Kaczmarek.
Understanding of the molecular underpinnings of synaptic plasticity is the major challenge of contemporary neurobiology, because this plasticity plays pivotal role in such phenomena as e.g.: learning and memory, neuronal regeneration, epileptogenesis and psychiatric disorders. So far, the vast majority of the studies on the plasticity has been focused on intercellular mechanisms. Recently, however, a role of extracellular matrix (ECM) in this context has also been appreciated. Notably, this is of particular importance as far as potential therapies are concerned, for an obvious reason of greatly facilitated access of the prospective drugs that might not need to penetrate into the cells.
L. Kaczmarek and his colleagues have initiated studies on ECM proteases in the physiology of the central nervousu system. The awarded pioneering research was focused on MMP-9.
In particular they showed that:
MMP-9 is necessary for long-term plasticity, learning and memory in animals;
MMP-9 is involved in aberrant plasticity underlying epileptogenesis;
The novel mechanisms governing MMP-9 gene expression have also been revealed. In conclusion, the results of these studies significantly advanced our fundamental knowledge on brain function as well as opened new avenues of research on new therapies of the most debilitating brain diseases.
The awarded team received the award from the hands of the Chairman of Division II of the Polish Academy of Science Prof. Andrzej B. Legocki on December 17, 2009 at the Division premises in the Palace of Culture and Science in Warsaw.
List of awarded publications:
1. Nagy, V., Bozdagi, O., Matynia, A., Balcerzyk, M., Okulski, P., Dzwonek, J., Costa, R.M., Silva, A.J., Kaczmarek, L., Huntley, G.W. Matrix metalloproteinase (MMP-9) is required for hippocampal late-phase LTP and memory. J. Neurosci., 26: 1923-1934, 2006.
2. Okulski P., Jay T.M., Jaworski J., Duniec K., Dzwonek J., Konopacki F.A., Wilczynski G.M., Sánchez-Capeli A., Mallet J., Kaczmarek L., TIMP-1 abolishes MMP-9-dependent long-lasting LTP in the prefrontal cortex. Biol. Psych., 62: 359-362, 2007.
3. Michaluk P., Kaczmarek L., Matrix metalloproteinase-9 (MMP-9) in glutamate-dependent adult brain function and dysfunction, Cell Death Differ., 14: 1255-1258, 2007.
4. Michaluk P., Kolodziej L., Mioduszewska B., Wilczynski G.M., Dzwonek J., Jaworski J., Gorecki D.C., Ottersen O.P., Kaczmarek L., b-dystroglycan as a target for MMP-9, in response to enhanced neuronal activity. J. Biol. Chem., 282: 16036-16041, 2007.
5. Konopacki F.A., Rylski M., Wilczek E., Amborska R., Detka D., Kaczmarek L., Wilczyński G.M., Synaptic localization of seizure-induced matrix metalloproteinase-9 mRNA. Neuroscience, 150: 31-39, 2007.
6. Wilczynski G.M., Konopacki F.A., Wilczek E., Lasiecka Z., Gorlewicz A., Michaluk P., Wawrzyniak M., Malinowska M., Okulski P., Kolodziej L.R., Konopka W., Duniec K., Mioduszewska B., Nikolaev E., Walczak A., Owczarek D., Gorecki D.C., Zuschratter W., Ottersen O.P., Kaczmarek L. Important role of matrix metalloproteinase 9 (MMP-9) in epileptogenesis. J. Cell Biol., 180: 1021-1035, 2008.
7. Gawlak M., Górkiewicz T., Gorlewicz A., Konopacki F.A., Kaczmarek L., Wilczynski G.M. High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses, Neuroscience, 158: 167-176, 2009.
8. Rylski M., Amborska A., Zybura K., Mioduszewska B., Michaluk P., Jaworski J., Kaczmarek L. Yin Yang 1 is a critical repressor of matrix metalloproteinase-9 expression in brain neurons. J. Biol. Chem., 283: 35140-35153, 2008.
9. Rylski M., Amborska R., Zybura K., Michaluk P., Bielinska B., Konopacki F.A.,. Wilczynski G.M., Kaczmarek L., JunB is a repressor of MMP-9 transcription in depolarized rat brain neurons. Mol. Cell. Neurosci., 40: 98-110, 2009. Epub: 2008 Oct 11.
10. Wilczynski G.M., Kaczmarek L. MMP-9/TIMP-1 Extracellular Proteolytic System as AP-1 Target in Response to Neuronal Activity. W: Transcriptional Regulation by Neuronal Activity: To the Nucleus and Back (Dudek S., red.). Springer, 2008, str. 277-294.