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Neuronal TDP-43 depletion affects activity-dependent plasticity

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cris.lastimport.scopus2024-02-12T20:09:01Z
dc.abstract.enTAR 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 cyclothiazidedependent 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.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKnapska, Ewelina
dc.contributor.authorBulska, Ewa
dc.contributor.authorKonopka, Anna
dc.contributor.authorGórkiewicz, Tomasz
dc.contributor.authorElguera, Julio Torres
dc.contributor.authorBijoch, Łukasz Damian
dc.contributor.authorBEROUN, ANNA
dc.contributor.authorKonopka, Witold
dc.contributor.authorKoza, Paulina
dc.date.accessioned2024-01-25T13:44:40Z
dc.date.available2024-01-25T13:44:40Z
dc.date.issued2019
dc.description.financeNie dotyczy
dc.description.volume130
dc.identifier.doi10.1016/J.NBD.2019.104499
dc.identifier.issn0969-9961
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/113513
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofNeurobiology of Disease
dc.relation.pagesart.no. 104499
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enTDP-43
dc.subject.enAMPA receptors
dc.subject.enFLOP/FLIP splice variants
dc.subject.enPTZ model
dc.titleNeuronal TDP-43 depletion affects activity-dependent plasticity
dc.typeJournalArticle
dspace.entity.typePublication