title: Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density.
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.
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33620, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Rogers
authors.forename: Ian
authors.initials: I
authors.lastname: Rusiana
authors.forename: Justin
authors.initials: J
authors.lastname: Trotter
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhao
authors.forename: Erika
authors.initials: E
authors.lastname: Donaldson
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
authors.forename: Lenard W
authors.initials: LW
authors.lastname: Babus
authors.forename: Melinda
authors.initials: M
authors.lastname: Peters
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Banko
authors.forename: Pascale
authors.initials: P
authors.lastname: Chavis
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000166:cytology*; D050882:CREB-Binding Protein / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D049229:Dendritic Spines / Q000187:drug effects* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000523:psychology; D057809:HEK293 Cells / Q000166:cytology; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000648:ultrastructure*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000494:pharmacology*; D016622:Silver Staining / Q000379:methods
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D050882:CREB-Binding Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases