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

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.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2016
Accession Number
AD1020665

Entities

People

  • Jacob Raber
  • Joseph Weiss
  • Sydney Weber

Organizations

  • Oregon Health & Science University

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Central Nervous System
  • Cognitive Impairment
  • Genetic Phenomena
  • Genetics
  • Health Services
  • Hippocampus
  • Inhibition
  • Inhibitors
  • Learning
  • Medical Personnel
  • Mutations
  • Nervous System
  • Phenotypes
  • Students
  • Supervisors
  • Training

Fields of Study

  • Biology
  • Psychology

Readers

  • Molecular and genetic basis of cancer.
  • Neuroscience

Technology Areas

  • Biotechnology