Zebrafish as a Model to Study NF1-Associated Learning Deficits
Abstract
Neurofibromatosis type 1 (NF1) is a neurogenetic disorder best known to cause predisposition to central and peripheral nervous system tumors. At the same time, NF1 causes significant cognitive impairments, and 50-70% of children with NF1 exhibit cognitive dysfunction, most prominently scholastic under-performance characterized by attention deficit and learning disabilities. The NF1 protein govern distinct aspects of cognitive behavior: the NF1-GRD attenuates Ras-pathway and GABA signaling to regulate memory, while the NF1 C-terminal region activates adenylate cyclase - mediated cAMP homeostasis to govern learning. Despite clear evidence of cAMP-mediated learning in Drosophila Nf1 models, it is unclear whether NF1-dependent cAMP signaling is critical for vertebrate learning and/or memory. The aims of this proposal are to take advantage of the zebrafish system to 1) determine whether cAMP signaling contributes to NF1-dependent learning and memory in vertebrates and 2) identify compounds that attenuate the learning deficiency in NF1 through screening libraries of bioactive small molecules.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2016
- Accession Number
- AD1030132
Entities
People
- Michael Granato
Organizations
- University of Pennsylvania