NON-PEPTIDE ANALOGUE OF A FRAGMENT OF SOLUBLE ABETA PRECUSOR PROTEIN POTENTIATES WEAK MEMORY AND C-FOS EXPRESSION IN THE MOUSE BRAIN

DOI: https://doi.org/None

K.A. Toropova (1), O.I. Ivashkina (1), M.A. Roshchina (1), K.V. Vorobyev (2), E.V. Konovalova (2), V.G. Nenajdenko (3), A.A. Makhmutova (4), S.O. Bachurin (4), K.V. Anokhin (1,2) 1 -National Research Centre «Kurchatov Institute», Akademika Kurchatova Sq., 1, Moscow, 123182, Russian Federation; 2 -P.K. Anokhin Institute of Normal Physiology, Baltiiskaya Str., 8, Moscow, 125315, Russian Federation; 3 -Lomonosov Moscow State University, Leninskiye Gory 1–3, Moscow, 119991, Russian Federation; 4 -Institute of Physiologically Active Compounds, Severny proyezd, 1, Chernogolovka, 142432, Russian Federation

Introduction. Short-term and long-term memory impairments are the main symptoms of several socially important neurodegenerative disorders, such as Alzheimer disease. For this purpose the pharmacological enhancement of short-term memory is of great interest. Non-peptide mimetics of soluble APP protein, that mimic its biological function in synaptic plasticity and memory formation, are the one of new promising approaches to develop cognitive enhancers for Alzheimers disease. However little is known about their action in the brain and their effects on short-term memory. Purpose of research was to evaluate possible promnestic action of sAPP-mimetic P2 on the short-term memory and to study targets of its effects in the mouse brain. Methods. Experiments were performed on the adult male C57Bl/6 mice trained in one of three models of weak memory: immediate shock deficit, weak contextual fear conditioning or trace fear conditioning. Mice were injected i.p. with P2 (0,5 mg/kg) or saline 30 min prior to training. Memory was tested 2 or 24 h after the training. Cellular targets of P2 promnestic effect were investigated by immunohistochemical mapping of immediate early gene c-fos activity in the brain. Results. P2 injection prior to training resulted in significant enhancement of weak memory tested 2 h after training in the immediate shock deficit task. P2 injection increased c-fos expression in the retrosplenial cortex (disgranular part), parietal association cortex and hippocampal CA3. Conclusion. Mimetic of sAPP P2 stimulates weak short-term memory in immediate shock deficit task and enhances c-fos immediate early gene expression in the mouse brain.
Keywords: 
weak memory, cognitive enhancer, immediate early gene c-fos, fear conditioning
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