IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Biochemical evidence for altered protein levels of plasticity-related genes in inducible TDP- 43- ΔNLS transgenic mice.
Autor/es:
KATCHE C; ALFIERI, J; DE LANDETA, AB; MULLER IGAZ, L
Reunión:
Congreso; XXXII Reunión Anual Sociedad Argentina de Investigación en Neurociencia; 2017
Resumen:
Mislocalization and aggregation of the nuclear protein TDP-43 are hallmark features of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We have shown in mice that inducible overexpression of a cytoplasmically-localized form of TDP-43 (TDP-43-ΔNLS) in forebrain neurons recapitulates several features of TDP-43 proteinopathies. Here, we focus on plasticity-related genes (PRGs) which are key for normal cognition, a function affected in both human disease and our mouse model. Using gene expression data from microarray studies in TDP-43-ΔNLS brain tissue as a springboard, we identified decreased mRNA levels of Zif268, c-fos and Arc, PRGs critically involved in cognitive function and neural plasticity. These changes were corroborated by immunofluorescence analysis of TDP- 43-ΔNLS cortical and hippocampal tissue. Here, we complement this data using immunoblot analysis and investigate in TDP-43 mice the protein levels of BDNF, a neurotrophin with key functions in plasticity. We found that Zif268 protein levels are dramatically decreased in TDP-43-ΔNLS brain, while exposure to a behavioural challenge such as an open field does not elicit proper PRG induction in these mice. Remarkably, BDNF protein levels are increased in TDP-43-ΔNLS brain, suggesting a compensatory mechanism involving this neurotrophin. These results indicate that abnormal PRG protein levels may underlie the behavioural abnormalities in TDP-43 related pathologies.