title: Deleterious effects of soluble beta amyloid on cognition, antagonism by saline and noradrenaline, a role for microglia.
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.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, 399 Royal Parade, Parkville, Victoria 3052, Australia. marie.gibbs@monash.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Gibbs
authors.forename: C L
authors.initials: CL
authors.lastname: Gibbs
mesh_terms: D000322:Adrenergic Agonists / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity*; D012054:Reinforcement, Psychology; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000322:Adrenergic Agonists; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D012965:Sodium Chloride