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

MARIANA VALLEJO ; SEBASTIÁN LOYOLA; DARWIN CONTRERAS; GONZALO UGARTE; DIEGO CIFUENTE; GABRIELA ORTEGA; JOSÉ L. CABRERA; MARC ZEISE; CARLOS TONN; MARIO CARREÑO; BERNARDO MORALES ; MARIEL AGNESE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 129 p. 864 - 864

bstract Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and their chemical structures were analyzed by NMR. While monoacetyl sauroine is the typical product of acetylation, DAS is an unexpected derivative related to the keto-enol formation of sauroine. Recordings of field excitatory post-synaptic potentials 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 lM. This effectwasblockedby10 lMD(-)-2-amino-5-phosphonopentanoic acid (AP5), suggesting dependence on the NMDA receptor. DAS significantly increased NMDA receptor-dependent excitatory post-synaptic currents without affecting a-amino- 3-hydroxy-5-methylisoxazole-4-propionate receptor-dependent currents. Repetitive administration of DAS improved visuospatial learning in the Morris Water