Institute of Fundamental Technological Research
Polish Academy of Sciences


Leszek Kaczmarek

Supervision of doctoral theses
1.  2016-06-24 Koza Paulina  
The effects of TDP-43 depletion on neuronal plasticity in Syn-TDP-43WT transgenic rat model 

Recent publications
1.  Rinoldi C., Ziai Y., Zargarian Seyed S., Nakielski P., Zembrzycki K., Haghighat Bayan Mohammad A., Zakrzewska A., Fiorelli R., Lanzi M., Kostrzewska-Księżyk A., Czajkowski R., Kublik E., Kaczmarek L., Pierini F., In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface, ACS Applied Materials and Interfaces, ISSN: 1944-8244, DOI: 10.1021/acsami.2c17025, Vol.15, No.5, pp.6283-6296, 2023

In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain–computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today’s major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

brain−machine interface,conductive hydrogels,nanostructured biomaterials,in vitro and in vivo biocompatibility,long-term neural recording

Rinoldi C. - IPPT PAN
Ziai Y. - IPPT PAN
Zargarian Seyed S. - IPPT PAN
Nakielski P. - IPPT PAN
Zembrzycki K. - IPPT PAN
Haghighat Bayan Mohammad A. - IPPT PAN
Zakrzewska A. - IPPT PAN
Fiorelli R. - IPPT PAN
Lanzi M. - University of Bologna (IT)
Kostrzewska-Księżyk A. - other affiliation
Czajkowski R. - other affiliation
Kublik E. - other affiliation
Kaczmarek L. - other affiliation
Pierini F. - IPPT PAN
2.  Koza P., Beroun A., Konopka A., Górkiewicz T., Bijoch Ł., Torres J.C., Bulska E., Knapska E., Kaczmarek L., Konopka W., Neuronal TDP-43 depletion affects activity-dependent plasticity, Neurobiology of Disease, ISSN: 0969-9961, DOI: 10.1016/j.nbd.2019.104499, Vol.130, pp.104499-1-12, 2019

TAR DNA-binding protein 43 (TDP-43) is a hallmark of some neurodegenerative disorders, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43-related pathology is characterized by its abnormally phosphorylated and ubiquitinated aggregates. It is involved in many aspects of RNA processing, including mRNA splicing, transport, and translation. However, its exact physiological function and role in mechanisms that lead to neuronal degeneration remain elusive. Transgenic rats that were characterized by TDP-43 depletion in neurons exhibited enhancement of the acquisition of fear memory. At the cellular level, TDP-43-depleted neurons exhibited a decrease in the short-term plasticity of intrinsic neuronal excitability. The induction of long-term potentiation in the CA3-CA1 areas of the hippocampus resulted in more stable synaptic enhancement. At the molecular level, the protein levels of an unedited (R) FLOP variant of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR1 and GluR2/3 subunits decreased in the hippocampus. Alterations of FLOP/FLIP subunit composition affected AMPAR kinetics, reflected by cyclothiazide-dependent slowing of the decay time of AMPAR-mediated miniature excitatory postsynaptic currents. These findings suggest that TDP-43 may regulate activity-dependent neuronal plasticity, possibly by regulating the splicing of genes that are responsible for fast synaptic transmission and membrane potential.

TDP-43, AMPA receptors, FLOP/FLIP splice variants, PTZ model

Koza P. - other affiliation
Beroun A. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Konopka A. - University of Warsaw (PL)
Górkiewicz T. - other affiliation
Bijoch Ł. - other affiliation
Torres J.C. - other affiliation
Bulska E. - other affiliation
Knapska E. - other affiliation
Kaczmarek L. - other affiliation
Konopka W. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
3.  Stefaniuk M., Gualda E.J., Pawlowska M., Legutko D., Matryba P., Koza P., Konopka W., Owczarek D., Wawrzyniak M., Loza-Alvarez P., Kaczmarek L., Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/srep28209, Vol.6, pp.28209-1-9, 2016

Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior over passive CLARITY and CUBIC methods. Finally, we demonstrate efficient imaging of the rat brain using light-sheet fluorescence microscopy.

Stefaniuk M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Gualda E.J. - Barcelona Institute of Science and Technology (ES)
Pawlowska M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Legutko D. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Matryba P. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Koza P. - other affiliation
Konopka W. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Owczarek D. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Wawrzyniak M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Loza-Alvarez P. - Barcelona Institute of Science and Technology (ES)
Kaczmarek L. - other affiliation

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