Role of Non-neuronal Cells in Tauopathies After Brain Injury
Abstract
This study attempts to address a major knowledge gap, the role of inflammatory complement proteins, which are elevated during a prolonged asymptomatic period in mild repeated traumatic brain injury (rmTBI), in chronic traumatic encephalopathy (CTE). Current CTE models recapitulate some but not some of the key features, which may in part due to the lack of sulci in the mouse brain where in humans the pathology begins, specifically perivascular tau pathology. We predict that novel transgenics model overexpressing specific inflammatory proteins in mice subjected to repeat lateral mild, head trauma model may better recapitulate CTE. We used three transgenic models to examine responses to rmTBI, one that accumulates C1q (Serpin KO) and that accumulates C5a, a by product of the neurotoxic complement cascade and a model of human tau overexpression. Bigenic tau mice showed low viability, so we developed a htau bigenic that overexpressed the astrocyte protein MEGF10 responsible of removal of synapses including synaptic tau, and showed deficits. The outcomes of this study included identified rmTBI-dependent plasma biomarkers in brain derived vesicles ( ER stress marker BIP/GRP78,GFAP, tau and Aqp4, an astrocytic endfeet protein on vessels). We showed tg-dependent locomotor disturbances associated with neuroinflammatory pathology and increased perivascular glial tau and abnormal distribution of AQP4 as well as demyelination. Despite poor viability of serpinKO-tau bigenic, the serpinKO alone appears to develop tau and warrant future investigation. This study should produce 4 publications and provide data to support new funding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2019
- Accession Number
- AD1097351
Entities
People
- Sally A Frautschy
Organizations
- University of California, Los Angeles