title: Neuron-Targeted Caveolin-1 Improves Molecular Signaling, Plasticity, and Behavior Dependent on the Hippocampus in Adult and Aged Mice.
abstract: Studies in vitro demonstrate that neuronal membrane/lipid rafts (MLRs) establish cell polarity by clustering progrowth receptors and tethering cytoskeletal machinery necessary for neuronal sprouting. However, the effect of MLR and MLR-associated proteins on neuronal aging is unknown.
  
  
  
  Here, we assessed the impact of neuron-targeted overexpression of an MLR scaffold protein, caveolin-1 (Cav-1) (via a synapsin promoter, SynCav1), in the hippocampus in vivo in adult (6-month-old) and aged (20-month-old) mice on biochemical, morphologic, and behavioral changes.
  
  
  
  SynCav1 resulted in increased expression of Cav-1, MLRs, and MLR-localization of Cav-1 and tropomyosin-related kinase B receptor independent of age and time post gene transfer. Cav-1 overexpression in adult mice enhanced dendritic arborization within the apical dendrites of hippocampal cornu ammonis 1 and granule cell neurons, effects that were also observed in aged mice, albeit to a lesser extent, indicating preserved impact of Cav-1 on structural plasticity of hippocampal neurons with age. Cav-1 overexpression enhanced contextual fear memory in adult and aged mice demonstrating improved hippocampal function.
  
  
  
  Neuron-targeted overexpression of Cav-1 in the adult and aged hippocampus enhances functional MLRs with corresponding roles in cell signaling and protein trafficking. The resultant structural alterations in hippocampal neurons in vivo are associated with improvements in hippocampal-dependent learning and memory. Our findings suggest Cav-1 as a novel therapeutic strategy in disorders involving impaired hippocampal function.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD.|Committee on the Neurobiology of Addictive Disorders, TSRI.
authors.forename: Chitra D
authors.initials: CD
authors.lastname: Mandyam
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schilling
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.|Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University.
authors.forename: Weihua
authors.initials: W
authors.lastname: Cui
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Junji
authors.initials: J
authors.lastname: Egawa
authors.affiliation: Department of Cellular and Molecular Medicine, UCSD, Sanford Consortium for Regenerative Medicine.
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Niesman
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kellerhals
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, TSRI.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Staples
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Busija
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Psychiatry, UCSD.
authors.forename: Victoria B
authors.initials: VB
authors.lastname: Risbrough
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Edmund
authors.initials: E
authors.lastname: Posadas
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Grace C
authors.initials: GC
authors.lastname: Grogman
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Jamie W
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Patel
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.affiliation: Veterans Affairs San Diego Healthcare System.|Department of Anesthesiology, UCSD.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Head
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D021381:Protein Transport; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction; D016704:Synapsins / Q000235:genetics
chemical_list: D051242:Caveolin 1; D016704:Synapsins; D002772:Cholera Toxin; D020813:Receptor, trkB
keywords: CA1; Caveolin; Dentate gyrus; Membrane/lipid rafts; Neuroplasticity; TrkB