Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk

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E. Knapska


Ostatnie publikacje
1.  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

Streszczenie:
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.

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

Afiliacje autorów:
Koza P. - inna afiliacja
Beroun A. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Konopka A. - Uniwersytet Warszawski (PL)
Górkiewicz T. - inna afiliacja
Bijoch Ł. - inna afiliacja
Torres J.C. - inna afiliacja
Bulska E. - inna afiliacja
Knapska E. - inna afiliacja
Kaczmarek L. - inna afiliacja
Konopka W. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
100p.

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