title: Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice.
abstract: Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease. To test this hypothesis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 (APP/PS1) mice using the agonist clenbuterol (intraperitoneal injection, 2 mg/kg). We found that β2-adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines. These effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice.
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China.
authors.forename: Gao-Shang
authors.identifier: 0000-0002-1943-3717
authors.initials: GS
authors.lastname: Chai
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China.
authors.forename: Amina
authors.initials: A
authors.lastname: Yasheng
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
keywords: APP/PS1 mice; Alzheimer's disease; amyloid β; clenbuterol; dendritic spine; memory; nerve regeneration; neural regeneration; neurogenesis; postsynaptic density 95; synapsin 1; synaptophysin; β2-adrenoceptors