Memory loss caused by β-amyloid protein is rescued by a β3-adrenoceptor agonist

Gibbs, Marie E.; Maksel, Danuta; Gibbs, Zoe; Hou, Xu; Summers, Roger J.; Small, David H.

doi:10.1016/j.neurobiolaging.2008.05.018

« Previous Next »Neurobiology of Aging
Volume 31, Issue 4 , Pages 614-624, April 2010

Memory loss caused by β-amyloid protein is rescued by a β₃-adrenoceptor agonist

Marie E. Gibbs
- Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Wellington Road, Clayton, Victoria 3800, Australia
- Corresponding author. Tel.: +61 3 9905 2714; fax: +61 3 9905 8192.
Danuta Maksel
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
Zoe Gibbs
- Department of Psychology, Monash University, Clayton, Victoria 3800, Australia
Xu Hou
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
Roger J. Summers
- Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
David H. Small
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
- Menzies Research Institute, Hobart, Tasmania 7000, Australia

Received 30 December 2007; received in revised form 20 April 2008; accepted 21 May 2008. published online 21 July 2008.

Abstract

Accumulation of the neurotoxic β-amyloid protein (Aβ) in the brain is a key step in the pathogenesis of Alzheimer's disease (AD). Although transgenic mouse models of AD have been developed, there is a clear need for a validated animal model of Aβ-induced amnesia which can be used for toxicity testing and drug development. Intracranial injections of Aβ_1–42 impaired memory in a single trial discriminative avoidance learning task in chicks. Memory inhibition was closely associated with the state of aggregation of the Aβ peptide, and a scrambled-sequence of Aβ_1–42 peptide failed to impair memory. Aβ had little effect on labile (short-term and intermediate) memory, but blocked consolidation of memory into long-term storage mimicking the type of anterograde amnesia that occurs in early AD. Since noradrenaline exerts a modulatory influence on labile memory in the chick, we examined the effects of two β-adrenoceptor (AR) agonists on Aβ-induced amnesia. A β₃-AR agonist (CL316243), but not a β₂-AR agonist, rescued Aβ-induced memory loss, suggesting the need for further studies on the role of β₃-ARs in AD.

Keywords: Chick, Amyloid, Abeta, Dementia, Memory, Alzheimer's disease, Neurotoxicity, Passive avoidance