title: Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse.
abstract: The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory. Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia. HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition. The present studies test the hypothesis that in vivo elevation of Reelin levels can rescue synaptic and behavioral phenotypes associated with HRM. We demonstrate that a single in vivo injection of Reelin increases GAD67 expression and alters dendritic spine morphology. In parallel we observed enhancement of hippocampal synaptic function and associative learning and memory. Reelin supplementation also increases pre-pulse inhibition. These results suggest that characteristics of HRM, similar to those observed in schizophrenia, are sensitive to Reelin levels and can be modified with Reelin supplementation in male and female adults.
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Rogers
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhao
authors.forename: Justin H
authors.initials: JH
authors.lastname: Trotter
authors.forename: Ian
authors.initials: I
authors.lastname: Rusiana
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Peters
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Li
authors.forename: Erika
authors.initials: E
authors.lastname: Donaldson
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Banko
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Keenoy
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Arcangelo
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism; D007858:Learning; D007859:Learning Disabilities / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055139:Sensory Gating; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1