Gibbs_Neuro_Aging.pdf (667.77 kB)
Memory loss caused by ß-amyloid protein is rescued by aß3-adrenoceptor agonist
journal contributionposted on 2023-05-16, 23:16 authored by Gibbs, ME, Maksel, D, Gibbs, Z, Hou, X, Summers, RJ, David SmallDavid Small
Accumulation of the neurotoxic Î²-amyloid protein (AÎ²) 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 AÎ²-induced amnesia which can be used for toxicity testing and drug development. Intracranial injections of AÎ²1-42 impaired memory in a single trial discriminative avoidance learning task in chicks. Memory inhibition was closely associated with the state of aggregation of the AÎ² peptide, and a scrambled-sequence of AÎ²1-42 peptide failed to impair memory. AÎ² 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 Î²-adrenoceptor (AR) agonists on AÎ²-induced amnesia. A Î²3-AR agonist (CL316243), but not a Î²2-AR agonist, rescued AÎ²-induced memory loss, suggesting the need for further studies on the role of Î²3-ARs in AD. Â© 2008 Elsevier Inc.
Publication titleNeurobiology of Aging
Department/SchoolMenzies Institute for Medical Research
Place of publicationUSA