An acetylated sauroine derivative generates Chem LTP

M.G. VALLEJO; M.G. ORTEGA; S. LOYOLA; C. ROZAS; D.A. CIFUENTE; C. ARDANAZ; J.L. CABRERA; C.E. TONN; B. MORALES; A.M. AGNESE

Ribeirao Preto, Brasil

Simposio; 4th International Symposium of research and Posgraduation; 2010

Universidad de Sao Paulo

In previous works, we showed that sauroine (Sr) an alkaloid from Huperzia saururus (Lam.) Trevis. strongly enhances hippocampal Long Term Potentiation (LTP) and memory retention demonstrated in vivo, but did not inhibit the  acetylcholinesterase (AChE) enzyme. On contrary, sauroxine, another alkaloid, inhibited AChE but had no effect on LTP. These results conducted us to investigate which is the pharmacophore that promotes activity on memory. Thus, we obtained different Sr derivatives and assayed two acetylated derivatives, A2 and A3, and a reduced one, R2, to discover if they generate LTP. Sprague-Dawley rats (20 d, 60-70g) were sacrificed, hippocampi was dissected out and slices were cut. Under artificial physiological conditions, Schaffer collaterals were stimulated and recordings were taken from CA1 stratum radiatum. After 20 min of baseline a high frequency stimuli (TBS, 5trains, 5hz) was applied to generate LTP and recordings continued  60 min post TBS. Controls were perfused with ACSF and also treatment plus A2, A3 and R2 (3 µM), respectively. Results showed that A2 and R2 (n=3) did not produce any significant difference compared to control (n=4). A3 (n=3) had a different behavior, it produced an increment in synaptic efficacy without TBS application, unlike controls, that needed the TBS to generate LTP (p<0.05). This phenomenon is known as Chem LTP.  We obtained new approaches to pharmacophoric structure of sauroine and contribution to new bioactive drug knowledge with potential use in neurodegenerative diseases.