title: β1-adrenergic receptor activation enhances memory in Alzheimer's disease model.
abstract: OBJECTIVE
  Deficits in social recognition and learning of social cues are major symptoms of neurodegenerative disorders such as Alzheimer's disease (AD). Here we studied the role of β1-noradrenergic signaling in cognitive function to determine whether it could be used as a potential therapeutic target for AD.
  
  
  METHODS
  Using pharmacological, biochemical and behavioral tools, we assessed social recognition and the β1-adrenergic receptor (ADR) and its downstream PKA/phospho-CREB (pCREB) signaling cascade in the medial amygdala (MeA) in Thy1-hAPPLond/Swe+(APP) mouse model of AD.
  
  
  RESULTS
  Our results demonstrated that APP mice display a significant social recognition deficit which is dependent on the β1-adrenergic system. Moreover, betaxolol, a selective β1-ADR antagonist, impaired social but not object/odor learning in C57Bl/6 mice. Our results identifies activation of the PKA/pCREB downstream of β1-ADR in MeA as responsible signaling cascade for learning of social cues in MeA. Finally, we found that xamoterol, a selective β1-ADR partial agonist, rescued the social recognition deficit of APP mice by increasing nuclear pCREB.
  
  
  CONCLUSIONS
  Our data indicate that activation of β1-ADR in MeA is essential for learning of social cues, and that an impairment of this cascade in AD may contribute to pathogenesis and cognitive deficits. Therefore, selective activation of β1-ADR may be used as a therapeutic approach to rescue memory deficits in AD. Further safety and translational studies will be needed to ensure the safety of this approach.
authors.affiliation: Behavioral and Functional Neuroscience Laboratory, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Coutellier
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA ; Behavioral and Functional Neuroscience Laboratory, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Pooneh Memar
authors.initials: PM
authors.lastname: Ardestani
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA ; Behavioral and Functional Neuroscience Laboratory, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Shamloo
keywords: Alzheimer’s disease; CREB phosphorylation; cognitive enhancers; medial amygdala; memory; social recognition; β1-adrenergic receptor