Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease

  • Neural Regen Res. 2017 Sep;12(9):1499-1506. doi: 10.4103/1673-5374.215261.
Qin Wu  1  2 ,  Jin-Xia Sun  2 ,  Xiang-He Song  2 ,  Jing Wang  2 ,  Cun-Quan Xiong  2 ,  Fei-Xiang Teng  2 ,  Cui-Xiang Gao  2
Affiliations
  • 1. Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
  • 2. College of Medical Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu Province, China.
PMID: 29089997 DOI: 10.4103/1673-5374.215261
Abstract

Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrenergic receptor increased Amyloid-β accumulation by downregulating hippocampal α-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.

Keywords
Alzheimer's disease; ICI 118551; amyloid precursor protein; amyloid-β; beta-2 adrenergic receptor; cognitive function; dendrite ramification; nerve regeneration; neural regeneration; neurodegeneration; synapsin 1; synaptophysin; α-secretase.
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