Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density

  1. Edwin J. Weeber1,2,12
  1. 1Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33620, USA
  2. 2USF Health Byrd Alzheimer's Institute, Tampa, Florida 33613, USA
  3. 3Department of Molecular Biophysics and Physiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
  4. 4Department of Pharmacology, Georgetown University, Washington, DC 20057, USA
  5. 5Department of Neuroscience, Georgetown University, Washington, DC 20057, USA
  6. 6Department of Molecular Medicine, University of South Florida, Tampa, Florida 33620, USA
  7. 7Inserm Unité 901, Marseille 13009, France
  8. 8Université de la Méditerranée, UMR S901 Aix-Marseille 2, 13009, France
  9. 9INMED, Marseille 13009, France
  10. 10Department of Pharmacology, Georgetown University, Washington, DC 20057, USA
  11. 11Department of Neurology, Georgetown University, Washington, DC 20057, USA

    Abstract

    Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive function; however, the in vivo effect of enhanced Reelin signaling on cognitive function and synaptic plasticity in wild-type mice is unknown. The present studies test the hypothesis that in vivo enhancement of Reelin signaling can alter synaptic plasticity and ultimately influence processes of learning and memory. Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory. The present study suggests that an acute elevation of in vivo Reelin can have long-term effects on synaptic function and cognitive ability in wild-type mice.

    Footnotes

    • 12 Corresponding author.

      E-mail eweeber{at}health.usf.edu

    • [Supplemental material is available for this article.]

    • Received January 27, 2011.
    • Accepted June 23, 2011.
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