title: Activation of β2-adrenergic receptor promotes dendrite ramification and spine generation in APP/PS1 mice.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder, and currently there is no effective cure for this devastating disease. Decreases in the levels of β2-adrenoceptor (β2-AR) and norepinephrine have been reported in several regions of AD brains. The activation of β2AR can prevent the amyloid β (Aβ)-mediated inhibition of LTP (Long-term potentiation), but the mechanism is not fully understood. Here, we used APP/PS1 mice to study whether the activation of β2AR could remodel synaptic and/or dendritic plasticity. We found that the activation of β2AR by Clenbuterol (Clen) ameliorated memory deficits and promoted dendrite ramification and spine generation in hippocampal CA1 neurons, which was accompanied by the upregulation of postsynaptic density protein 95 (PSD95), synapsin 1 and synaptophysin. Conversely, the inhibition of β2AR by a siRNA blocked the Clen-induced increase in dendrite ramification and dendritic spines in primary hippocampal neurons. Furthermore, the activation of β2AR decreased cerebral amyloid plaques through the up-regulation of α-secretase activity and by decreasing the phosphorylation of APP at Thr668. Based on the roles of β2AR in dendrite ramification and spine generation, memory deficits and AD pathogenesis, compounds designed to activate β2AR might shed light on the cure of AD.
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 214122, PR China. Electronic address: chaigaoshang@jiangnan.edu.cn.
authors.forename: Gao-Shang
authors.initials: GS
authors.lastname: Chai
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 214122, PR 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, 214122, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 214122, PR China.
authors.forename: Amina
authors.initials: A
authors.lastname: Yasheng
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 214122, PR China. Electronic address: Zhaopeng336@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D018343:Receptors, Adrenergic, beta-2; D051528:Guanylate Kinases; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; Amyloid β; Clenbuterol; Dendrite ramification; Spine generation; β(2)-adrenoceptors