Open AccessBeta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer′s disease mice
Author(s) -
Gaoshang Chai,
Yangyang Wang,
Amina Yasheng,
Peng Zhao
Publication year - 2016
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.193241
Subject(s) - neurogenesis , synaptophysin , hippocampal formation , amyloid beta , neuroscience , amyloid precursor protein , neurodegeneration , dendritic spine , hippocampus , alzheimer's disease , medicine , psychology , disease , immunohistochemistry
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 β 2 -adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β 2 -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 β 2 -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 β 2 -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, β 2 -adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β 2 -adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice.