title: Cortistatin overexpression in transgenic mice produces deficits in synaptic plasticity and learning.
abstract: Cortistatin-14 (CST) is a neuropeptide expressed in cortical and hippocampal interneurons that shares 11 of 14 residues with somatostatin. In contrast to somatostatin, infusion of CST decreases locomotor activity and selectively enhances slow wave sleep. Here, we show that transgenic mice that overexpress cortistatin under the control of neuron-specific enolase promoter do not express long-term potentiation in the dentate gyrus. This blockade of dentate LTP correlates with profound impairment of hippocampal-dependent spatial learning. Exogenously applied CST to slices of wild-type mice also blocked induction of LTP in the dentate gyrus. Our findings implicate cortistatin in the modulation of synaptic plasticity and cognitive function. Thus, increases in hippocampal cortistatin expression during aging could have an impact on age-related cognitive deficits.
authors.affiliation: Department of Pharmacology and Physiology, Drexel University, University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Melanie K
authors.initials: MK
authors.lastname: Tallent
authors.forename: Véronique
authors.initials: V
authors.lastname: Fabre
authors.forename: Cuie
authors.initials: C
authors.lastname: Qiu
authors.forename: Marta
authors.initials: M
authors.lastname: Calbet
authors.forename: Tyra
authors.initials: T
authors.lastname: Lamp
authors.forename: Michael V
authors.initials: MV
authors.lastname: Baratta
authors.forename: Chisa
authors.initials: C
authors.lastname: Suzuki
authors.forename: Coree L
authors.initials: CL
authors.lastname: Levy
authors.forename: George R
authors.initials: GR
authors.lastname: Siggins
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Henriksen
authors.forename: José R
authors.initials: JR
authors.lastname: Criado
authors.forename: Amanda
authors.initials: A
authors.lastname: Roberts
authors.forename: Luis
authors.initials: L
authors.lastname: de Lecea
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007858:Learning / Q000502:physiology*; D007859:Learning Disabilities / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin