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 defcits in Alzheimer’s disease. To test this hypothesis, we investigated the e?ects 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 defcits, and increased dendritic branching and the density of dendritic spines. Tese e?ects 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 Tr668. Tese fndings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory defcits in APP/PS1 mice.

Key words: nerve regeneration, Alzheimer’s disease, β2-adrenoceptors, amyloid β, neurogenesis, clenbuterol, APP/PS1 mice, memory, dendritic spine, synapsin 1, synaptophysin, postsynaptic density 95, neural regeneration