Disorders of the Nervous System
Author: Gabriela Verónica Nieva | email: gabynieva@gmail.com
Gabriela Verónica Nieva 1°, Lionel Muller Igaz 1°
1° IFIBIO Houssay, Grupo de Neurociencia de Sistemas, Facultad de Medicina, Universidad de Buenos Aires – CONICET, Buenos Aires, Argentina
TDP-43 pathology is observed in a broad spectrum of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Activated microglial cells play an important role in immune and inflammatory responses in central nervous system and neurodegenerative diseases. Microglia-driven neuroinflammation is related with the onset of ALS/FTD and it is an important contributor to their pathogenesis and progression. After 1 month of post-weaning induction of the transgene, our mouse model conditionally overexpressing a cytoplasmic form of human TDP-43 (TDP-43-?NLS) in forebrain neurons recapitulate several of the motor, cognitive and social deficits observed in ALS-/FTD. Previously, we have shown that transgenic mice display higher levels of microglial activation in motor (MC) and somatosensory cortices (SSC) as well as hippocampal regions (CA1 and DG) compared to controls. To extend these findings, we now performed a quantitative assessment of microglial morphology using Iba1 immunofluorescence. We found longer perimeter and larger soma size in prefrontal cortex (PFC), MC and SSC, in addition to an increased number of Iba-1-labelled microglia in SSC. We are currently evaluating microgliosis in hippocampal subregions and performing Sholl analysis in all these brain areas in order to have more information about the branch complexity and the variations in microglial phenotypes. These results will help us elucidate the specific role of microglia in TDP-43 proteinopathies.