Accession Number : AD1020665


Title :   Effects of Pharmacologic and Genetic Inhibition of Alk on Cognitive Impairments in NF1 Mutant Mice


Descriptive Note : Technical Report,01 Jun 2013,31 May 2016


Corporate Author : Oregon Health and Science University Portland United States


Personal Author(s) : Raber,Jacob ; Weiss,Joseph ; Weber,Sydney


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1020665.pdf


Report Date : 01 Aug 2016


Pagination or Media Count : 17


Abstract : Concordant with studies in flies, we found enhanced retention of spatial memory in Alk mutant mice. Retention of spatial memory is a hippocampal dependent function. We also demonstrated expression of Alk throughout the adult murine hippocampus. The behavioral phenotype of Alk mutant mice is the opposite of the behavioral phenotype of NF1 mutant mice. Therefore, in this pilot project, we tested the hypothesis that the genetic interaction between Alk and Nf1 in mice is similar to the behavioral phenotypes of Alk and NF1 mutations in flies and that pharmacologic or genetic inhibition of Alk in NF1 mutant mice will attenuate or even rescue learning impairments in mice. We are excited to report that we have observed the predicted improvement in hippocampal-dependent cognitive function using both genetic and pharmacologic inhibition of Alk in heterozygous NF1 mutant mice. Our findings are consistent with the hypothesis that pharmacologic or genetic inhibition of Alk in NF1 mutant mice rescues their cognitive impairments.


Descriptors :   central nervous system , brain , clinical trials , therapeutics , mutations , PHARMACOLOGY , inhibition , memory , hippocampus , cognition , genetics , mice


Distribution Statement : APPROVED FOR PUBLIC RELEASE