A NEW SEMI-SYNTHETIC DERIVATIVE OF SAUROINE INDUCES LTP IN HIPPOCAMPAL SLICES AND IMPROVES LEARNING PERFORMANCE IN THE MORRIS WATER MAZE

M.G. VALLEJO; S. LOYOLA; D. CONTRERAS; G. UGARTE; D.A. CIFUENTE; M.G. ORTEGA; J.L. CABRERA; M. ZEISE; C.E. TONN; M. CARREÑO; R. DELGADO; B. MORALES; A. M. AGNESE

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 p. 864 - 876

0022-3042

Two semi-synthetic acetyl-derivatives of the alkaloid sauroine fromHuperzia saururus were obtained: Monoacetyl sauroine (MAS) and diacetylsauroine (DAS), and their chemical structures analyzed by NMR. While MAS isthe typical product of acetylation, DAS is an unexpected derivative related to theketo-enol formation of sauroine. Recordings of field EPSPs from the CA1 region of rat hippocampal slices showed that only DAS acutely applied induced chemical Long-Term Potentiation (LTP) in a dose-dependent manner with an EC50 of 1.15±0.09 μM. This effectwas blocked by 10 μM D(-)-2-amino-5-phosphonopentanoic acid (AP5), suggesting dependence on the NMDA receptor. DAS significantly increased NMDA receptor-dependent EPSCs without affecting AMPA receptor-dependent currents. Repetitive administration of DAS improved visuo-spatial learning in the Morris Water Maze (MWM). In slices from rats tested in the MWM, LTP resulting from electrical synaptic stimulation was 2.5 times larger than in controls. Concentration of DAS measured in the brain after repetitive administration was 29.5 μM. We conclude that slices perfused with DAS display a robust NMDA receptor-dependent chemical LTP. During chronic treatment DAS enhances learning abilities through a metaplastic mechanism as revealed by theaugmentation of LTP in slices. DAS, therefore, may be a promising compound as a nootropic therapeutic drug.