Research Area #3: Mouse brain slice cultures transduced with rAAV vectors as novel models of neurodegenerative disease
Dr. Cara Croft, now at UCL, developed our brain slice culture models when she was a postdoctoral fellow in the lab. We are now able to use rAAV vectors to transduce neurons, astrocytes microglial and oligodendroglia cells in these culture and keep them alive for 6-12 months. By delivering tau and a-synuclein transgenes we have been able to drive neurofibrillary pathology and Lewy Body like pathology, respectively. Further, using optical pulse chase studies, we can show that tau tangles turnover in the cell. We are extending these studies to try and better understand how tau and synuclein pathologies impact cellular functions, and to more rapidly identify modulators of pathology. Notably, this is one of the most reproducible paradigms in which we can transduce microglial cells with rAAV vectors. Current studies in the lab are led by Dr. Brenda Moore.
Key Publications: Croft et all JEM 2019, Croft et al , Acta Neuropath 2021
Funding NIH: RF1AG064914 U01TR003715
Key Collaborators: Dr. Cara Croft (UCL), Dr. Jada Lewis (UF), Dr. Karen McFarland, Dr. Shawn Hingtgen