Activation of beta(2)-adrenergic receptor promotes dendrite ramification and spine generation in APP/PS1 mice

作者：Chai, Gao-Shang^*; Wang, Yang-Yang; Zhu, Dan; Yasheng, Amina; Zhao, Peng^*

来源：Neuroscience Letters, 2017, 636: 158-164.

DOI：10.1016/j.neulet.2016.11.022

• Alzheimer's disease
• beta(2)-adrenoceptors
• Amyloid beta
• Dendrite ramification
• Spine generation
• Clenbuterol

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 beta(2)-adrenoceptor (beta(2)-AR) and norepinephrine have been reported in several regions of AD brains. The activation of beta(2)AR can prevent the amyloid beta (A beta)-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 beta(2)AR could remodel synaptic and/or dendritic plasticity. We found that the activation of beta(2)AR by Clenbuterol (Glen) 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 beta(2)AR by a siRNA blocked the Clen-induced increase in dendrite ramification and dendritic spines in primary hippocampal neurons. Furthermore, the activation of beta(2)AR decreased cerebral amyloid plaques through the up-regulation of a-secretase activity and by decreasing the phosphorylation of APP at Thr668. Based on the roles of beta(2)AR in dendrite ramification and spine generation, memory deficits and AD pathogenesis, compounds designed to activate beta(2)AR might shed light on the cure of AD.

• 出版日期2017-1-1
• 单位江南大学