REGIONAL AND TEMPORAL ASSESSMENT OF NEURODEGENERATION IN INDUCIBLE TDP-43-WT TRANSGENIC MICE.

SILVA PR; NIEVA GV; IGAZ LM

Mar del Plata

Congreso; XXXII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

Neurodegenerativediseases such as frontotemporal dementia (FTD) and amyotrophic lateralsclerosis (ALS) are characterized by neuronal inclusions mainly composed ofinsoluble Transactive Response DNA-binding Protein 43 (TDP-43). We developed atransgenic mice model with inducible overexpression of human wild-type TDP 43protein (hTDP-43-WT) in forebrain neurons, which recapitulate several featuresof TDP-43 proteinopathies. These animals develop time-dependent brain weightloss and dentate gyrus (DG) neurodegeneration. In the present study we analyzedin detail the region-specific neuronal loss, at early (1 month) and late (6months) time points of transgene (TG) induction. Using immunofluorescenceagainst NeuN (a marker of mature neurons), we measured the total width andNeuN-positive cell count in three cortical regions (motor, somatosensorial andprefrontal) and in two hippocampal structures (CA1 and DG). The results show mildneurodegeneration on prefontal cortex, CA1 and DG with absence of neuronal losson both motor and somatosensorial cortices after 1 month of TG induction. Theseresults are consistent with the early behavioral phenotype observed in hTDP-43-WTmice, displaying spatial and work memory deficits but normal motor performance.Preliminary results of the late time point in the same structures indicatesmore extensive neurodegeneration. Ours findings contribute to our understandingof the pathological mechanisms underlying these TDP-43 proteinopathies.