Accession Number : AD1030132


Title :   Zebrafish as a Model to Study NF1-Associated Learning Deficits


Descriptive Note : Technical Report,15 Apr 2014,14 Apr 2016


Corporate Author : University of Pennsylvania Philadelphia United States


Personal Author(s) : Granato,Michael


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1030132.pdf


Report Date : 01 Jul 2016


Pagination or Media Count : 21


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.


Descriptors :   fish , peripheral nervous system , learning , memory , dysfunction


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE