Region-specific features of early microglial activation in a conditional mouse model of TDP-43 proteinopathies

NIEVA GV; SILVA PR; IGAZ LM

Congreso; XXXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2021

Sociedad Argentina de Investigación en Neurociencias (SAN)

Microglia-driven neuroinflammation can play an important role in thepathophysiology of neurodegenerative disorders. We have shown that transgenicmice conditionally overexpressing human nuclear wild-type TDP-43 protein (hTDP-43-WT)in forebrain neurons, recapitulate key features of frontotemporaldementia (FTD) and amyotrophic lateral sclerosis (ALS). After 1 monthexpression of the transgene, this mouse model displays impairment in cognitiveand social behaviors in the absence of motor abnormalities. We previously describedearly-stage microglial activation inthese mice by analyzing fold change in percentage of Iba1+ area in selected cortical and hippocampal regions. Toextend these previous findings, we now performeda quantitative assessment of microglial morphology using Iba1 immunofluorescence.We found an increased number of Iba-1-labelled microglia in motor cortex (MC),in addition to longer perimeter and larger soma size in prefrontal (PFC),somatosensory (SSC) and motor cortices. Sholl analysis of microglia from MC andSSC revealed a reduction in branch complexity as we found a decrease in total processlength, fewer total intersections and a significant decrement in branching 16?20μm away from the soma, compared to control mice. In sum, these results detailing microglial morphological features expand our understanding of the relationship betweenearly-stage neuroinflammatory processes and behavioral deficits in TDP-43animal models of FTD/ALS.