REGIONAL ANALYSIS OF SYNAPTIC, AXONAL AND DENDRITIC MARKERS IN TRANSGENIC MICE EXPRESSING A MISLOCALIZED FORM OF TDP-43: IMPLICATIONS FOR ALS/FTD PATHOGENESIS.

VASSALLU, M. FLORENCIA; CALTANA, LAURA; IGAZ, LIONEL M.

Congreso; XXXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN).; 2022

Sociedad Argentina de Investigación en Neurociencias (SAN)

TDP-43 is the main component of thepathological cytoplasmic inclusions found in both amyotrophic lateral sclerosis(ALS) and frontotemporal dementia (FTD), two neurodegenerative diseases forwhich there is no known cure. TDP-43 is a protein localized in the nucleus andinvolved in RNA metabolism, among other functions. Our transgenic mice with induciblecytoplasmic expression of TDP-43 in forebrain neurons recapitulate behavioralphenotypes, neurodegeneration and gene expression changes that occur in bothdiseases. In order to evaluate the early effects of TDP-43-ΔNLS overexpression,we analyzed presynaptic markers Syntaxin 1 (Stx1) and Synaptophysin (Syn), andcytoskeleton proteins MAP2 (a protein associated to microtubule whoseexpression is specific to dendrites and cellular bodies) and NF200 (aneurofilament component and axonal marker). TDP-43-ΔNLS mice showed evidence ofdecreased hippocampal Stx1 immunoreactivity (IR) in mossy fiber terminalsprojecting to CA3 and Syn IR in hippocampal CA1 and auditory cortex, suggestingsynaptic loss. Study of IR levels for MAP2 and NF200 will reveal axonal anddendritic structure in different cortical areas and hippocampal subfields. Theanalysis of these neuronal markers will provide further evidence on the pathologicalabnormalities displayed by this animal model of TDP-43 proteinopathies, andhelp us to delineate the early events triggered by mislocalized TDP-43 beforeovert neurodegeneration is observed.