APP is required during an early phase of memory formation.
The amyloid beta/A4 protein precursor (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies, injected 30 min pretraining, prevented memory for a one-trial passive avoidance task in day-old chicks without effects on general behaviour or initial acquisition. Amnesia was apparent by 30 min post-training and lasted for at least 24 h. The same result was obtained by down-regulation of APP expression by APP-antisense, injected 8-12 h pretraining. However, injections of anti-APP antibodies or APP antisense at later post-training time did not cause amnesia for the task. Unlike antibodies and antisense, injection of the APP328-332 pentapeptide, in either orientation, 30 min pretraining, rescued the memory and prevented antisense-induced amnesia. The post-training time within which the antibody- and antisense-induced amnesia, and within which the APP peptides prevent amnesia, correspond to that during which memory formation is vulnerable to disruption of the putative signal transduction functions of APP. These results suggest that: (i) APP is required during an early phase of memory formation, and (ii) the memory enhancing effect of secretory APP is localized within a 5-mer sequence of growth-promoting domain.
Mileusnic
R
R
Brain and Behaviour Research Group, The Open University, Milton Keynes, MK7 6AA, UK. r.mileusnic@open.ac.uk
Lancashire
C L
CL
Johnston
A N
AN
Rose
S P
SP
D000647:Amnesia; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002645:Chickens; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013570:Synaptic Membranes / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D009842:Oligopeptides; D012333:RNA, Messenger