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

      Learning & memory (Cold Spring Harbor, N.Y.)
      Action Potentials, drug effects, Animals, Brain, cytology, CREB-Binding Protein, metabolism, Cell Adhesion Molecules, Neuronal, pharmacology, Cognition, Conditioning (Psychology), Dendritic Spines, ultrastructure, Excitatory Postsynaptic Potentials, Exploratory Behavior, Extracellular Matrix Proteins, Fear, psychology, HEK293 Cells, Humans, Maze Learning, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Serine Endopeptidases, Silver Staining, methods

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          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.

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