Alzheimer 2013 July-6

 

Deleterious effects of soluble beta amyloid on cognition, antagonism by saline and noradrenaline, a role for microglia.

Neuroscience. 2013 Jan 29;230:62-71.

Gibbs ME, Gibbs CL.

Monash Institute of Pharmaceutical Sciences, 399 Royal Parade, Parkville, Victoria 3052, Australia. marie.gibbs@monash.edu

Abstract

Small oligomeric beta amyloid (Aβ(1-42)) injected 45 min prior to single-trial bead discrimination training resulted in impaired learning in day-old chickens. A new experimental protocol was used where the injections of drugs were at times around the time of injection of Aβ. It was found that the Na(+) levels of the saline used to dissolve Aβ affected cognitive impairment. Na(+) levels above the normal plasma value (140 mM) reduced Aβ-induced learning deficits whereas levels below increased sensitivity to Aβ. The new protocol was also used to examine the ability of certain noradrenergic adrenoceptor antagonist and agonists, insulin, glucose and minocycline to reduce learning disruption caused by Aβ. The drugs (made up in 154 mM sodium chloride) were injected before, at the same time or after the injection of Aβ and although all drugs prevented Aβ-induced disruption of learning when given in the same injection as Aβ, some injected before could prevent Aβ disrupting learning, whereas others could rescue learning ability when given after Aβ injection. These results are interpreted in the light of possible actions of noradrenaline on microglia and various processes: astrocytic metabolism, cerebral microcirculation, and removal of Aβ away from the site of injection. The possible importance of hypernatremia and hyponatremia in the incidence of Alzheimer’s disease is discussed. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

PMID: 23168324

Marie Gibbs

As shown in the figure, lowering the concentration of sodium injected with the Ab resulted in Ab impairing memory at lower concentrations, i,e. hyponatremia increases sensitivity to Ab, whereas hypernatremia is protective. The experiments in this work provide further evidence for a role for noradrenaline in amelioration of the effects of Ab.

Although this work comes from day-old chicks, we believe it is likely to be relevant to the onset and in the ongoing progression of AD in man. Chicks have the same b-amyloid as found in humans, this is not the case for many other animal models.

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