Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome

Eur J Neurosci. 2015 May;41(10):1372-80. doi: 10.1111/ejn.12893. Epub 2015 Apr 13.

Abstract

The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain.

Keywords: behavior; cannulation; hippocampus; ubiquitin ligase; ventricle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / drug therapy
  • Angelman Syndrome / physiopathology*
  • Angelman Syndrome / psychology*
  • Animals
  • Cell Adhesion Molecules, Neuronal / administration & dosage*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cerebral Cortex / metabolism
  • Dendritic Spines / drug effects
  • Disease Models, Animal
  • Extracellular Matrix Proteins / administration & dosage*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • HEK293 Cells
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology
  • Hippocampus / ultrastructure
  • Humans
  • Injections, Intraventricular
  • Long-Term Potentiation / drug effects*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / administration & dosage*
  • Nerve Tissue Proteins / metabolism
  • Reelin Protein
  • Serine Endopeptidases / administration & dosage*
  • Serine Endopeptidases / metabolism
  • Spatial Learning / drug effects
  • Spatial Memory / drug effects

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • RELN protein, human
  • Reln protein, mouse
  • Serine Endopeptidases