ABNORMAL NEURON NUCLEAR MORPHOLOGY AFTER TRANSGENE SUPPRESSION IN A CONDITIONAL TDP-43 MOUSE MODEL OF NEURODEGENERATIVE DISEASE.

NIEVA GV; SILVA PR; IGAZ LM

Villa Carlos Paz, Cordoba

Congreso; XXXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Dysregulationof TDP-43 is a key feature of frontotemporal dementia (FTD) as well asamyotrophic lateral sclerosis (ALS). Previously, using a transgenic miceconditionally overexpressing human wild-type TDP-43 protein (hTDP-43-WT) weanalyzed the region-specific neuronal loss. We found a decrease in CA1 and dentategyrus (DG) NeuN+ cells width accompanied by decreased neuronal number,indicating mild neurodegeneration after 1 month transgene (TG) expression (1mo).In this study, we evaluated in this model the nuclear morphology of neuronsfrom hippocampal regions (DG and CA1), and somatosensory cortex layers after a TGsuppression protocol. We found an increased percentage of abnormal nuclei inthe suppressed group compared to controls and 1mo mice in all analyzed regions.This suggest that the cellular mechanisms coping with hTDP-43 overexpression andrecovery after suppression might differ. In this context, we are currently assessinghow TG suppression modulates neurodegeneration by evaluation of neuronalsurvival. Additionally, we studied the impact of corticospinal tract degeneration(observed in hTDP-43-NLS mice expressing a cytoplasmically-localized form inthe forebrain) on lower motor neuron (LMN) health in the spinal cord (SC). UsingNissl staining, we analyzed LMN area in the anterior horn from different SC segmentsand found no differences in TG TDP-43-NLS mice compared to controls. In summary,these results contribute to our understanding of FTD/ALS pathology.