F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice

Neuroscience. 2012 Oct 25;223:465-72. doi: 10.1016/j.neuroscience.2012.07.038. Epub 2012 Jul 31.

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia affecting the elderly. Evidence has emerged signifying that stimulation of the reelin pathway should promote neural plasticity and suppress molecular changes associated with AD, suggesting a potential therapeutic application to the disease. This was explored through the use of lentiviral vector-mediated overexpression of the reelin homolog, F-spondin, which is an activator of the reelin pathway. Intrahippocampal gene transfer of F-spondin improved spatial learning/memory in the Morris Water Maze and increased exploration of the novel object in the Novel Object Recognition test in wild-type mice. F-spondin overexpression also suppressed endogenous levels of amyloid beta (Aβ(42)) in these mice and reduced Aβ plaque deposition while improving synaptophysin expression in transgenic mouse models of AD. These data demonstrate pathologic and cognitive improvements in mice through F-spondin overexpression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Exploratory Behavior / physiology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix Proteins / therapeutic use*
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors / physiology
  • Green Fluorescent Proteins / genetics
  • Humans
  • Maze Learning / physiology
  • Memory Disorders / etiology
  • Memory Disorders / genetics*
  • Memory Disorders / therapy*
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Peptide Fragments / metabolism
  • Presenilin-1 / genetics

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Extracellular Matrix Proteins
  • F-spondin protein, mouse
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • amyloid beta-protein (1-42)
  • Green Fluorescent Proteins