Blocking beta2-adrenergic receptor attenuates acute stress-induced amyloid beta peptides production

Brain Res. 2010 Mar 4:1317:305-10. doi: 10.1016/j.brainres.2009.12.087. Epub 2010 Jan 6.

Abstract

Environmental factors play an important role in the Alzheimer's disease (AD) development and stress may accelerate the progression of AD. Beta-adrenergic receptors are activated by stress and may influence different aspects of cognitive function. So, it was hypothesized that stress may accelerate the pathological progression of AD by the activation of beta(2)-adrenergic receptor (beta(2)-AR). We have investigated the role of acute stress and activation of beta(2)-AR in amyloid beta (Abeta) peptides production in a mouse model of acute restraint stress. Injections of the beta(2)-AR-selective agonist clenbuterol hydrochloride enhanced the production of acute stress-induced Abeta peptides production; the beta(2)-AR-selective antagonist ICI 118,551 reduced Abeta peptides production. It is suggested that acute stress induces abnormal activation of beta(2)-AR which subsequently enhances Abeta peptides (the main neuropathological hallmarks of AD) production possibly resulting in the onset of AD. The findings indicate that new therapeutic strategies designed to blocking beta(2)-AR might be valuable for the prevention and treatment of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Alzheimer Disease
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Clenbuterol / pharmacology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / metabolism*
  • Propanolamines / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Random Allocation
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Restraint, Physical
  • Stress, Psychological / metabolism*

Substances

  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Propanolamines
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • ICI 118551
  • Clenbuterol