Tracy Hagemann

Credentials: PhD

Position title: Senior Scientist, Waisman Center

Email: tlhagemann@wisc.edu

Our research focuses on Alexander disease (AxD), a fatal neurodegenerative disorder caused by mutations in the gene for glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system. While onset can occur throughout the lifespan, the majority of cases manifest at an early age with motor and cognitive delays, encephalopathy, seizures, frequent emesis, and failure to thrive. We have generated a new rat model which develops normally during the first postnatal weeks but fails to thrive after weaning. AxD rats develop motor deficits as juveniles and show increased mortality with ~15% dying of unknown cause between 6-12 weeks. While the rat is a markedly improved model compared to our earlier mouse models, one of the common features among all rodent models is decreased body weight, the degree to which correlates with GFAP accumulation and astrocyte pathology in each line, with the rat being the most severe and exhibiting a cachexia-like phenotype. Astrocytes of the hypothalamus and brainstem play a critical role in central regulation of appetite and energy balance, and AxD rats demonstrate widespread pathology and astrogliosis. Investigating the association between dysfunctional astrocytes and failure to thrive will lead to a better understanding of AxD pathogenesis, and characterization of the metabolic phenotype in the new rat model is the focus of a pending R21 application. Given that cachexia involves many of the same mechanisms and pathways as diabetes, this research could lead to novel insights for both disorders.