title: Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity.
abstract: The role of α(1)-adrenergic receptors (α(1)ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α(1A)AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term α(1A)AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α(1A)AR. CAM-α(1A)AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α(1A)AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-α(1A)AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α(1A)AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-α(1A)AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α(1A)AR mice was 10% longer than that of WT mice. Our results suggest that long-term α(1A)AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.
authors.affiliation: Department of Pharmacology, Physiology & Therapeutics, School of Medicine & Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Van A
authors.initials: VA
authors.lastname: Doze
authors.forename: Robert S
authors.initials: RS
authors.lastname: Papay
authors.forename: Brianna L
authors.initials: BL
authors.lastname: Goldenstein
authors.forename: Manveen K
authors.initials: MK
authors.lastname: Gupta
authors.forename: Katie M
authors.initials: KM
authors.lastname: Collette
authors.forename: Brian W
authors.initials: BW
authors.lastname: Nelson
authors.forename: Mariaha J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Davis
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Luger
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Wood
authors.forename: James R
authors.initials: JR
authors.lastname: Haselton
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Perez
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: C547714:Adra1a protein, mouse; D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1