β1‐adrenergic receptor activation enhances memory in Alzheimer's disease model

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 β 1 ‐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 β 1 ‐adrenergic receptor ( ADR ) and its downstream protein kinase A ( PKA )/phospho‐cAMP response element‐binding protein (p CREB ) signaling cascade in the medial amygdala (MeA) in Thy1‐hAPP Lond/Swe+ ( APP ) mouse model of AD . Results Our results demonstrated that APP mice display a significant social recognition deficit which is dependent on the β 1 ‐adrenergic system. Moreover, betaxolol, a selective β 1 ‐ ADR antagonist, impaired social but not object/odor learning in C57Bl/6 mice. Our results identifies activation of the PKA /p CREB downstream of β 1 ‐ ADR in MeA as responsible signaling cascade for learning of social cues in MeA. Finally, we found that xamoterol, a selective β 1 ‐ ADR partial agonist, rescued the social recognition deficit of APP mice by increasing nuclear p CREB . Interpretation Our data indicate that activation of β 1 ‐ 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 β 1 ‐ 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.