Neurotoxicity induced by streptozotoxin: effects of angiotensin II AT1 receptor blocker upon memory.

MARINZALDA, M.; CASARSA, B; BREGONZIO, C; BAIARDI, G.

Uspallata

Congreso; V Neurotoxicity Society Meeting; 2011

Neurotoxicity Society

This study was designed to investigate the beneficial effect of a neuroprotective agent candesartan (CV) an Angiotensin II AT1 receptor blocker on intracerebroventricular (ICV) streptozotocin (STZ)-induced cognitive impairment in rats. For this purpose, 4 groups of adult male Wistar rats (n=10) were: 1) ICV injected with STZ (3 mg/kg) for 2 consecutive days + oral administration of CV vehicle. 2) were treated with same dosis of STZ + CV (3mg/kg/day) oral administration during a period of 7 days before and 9 days after STZ injection. 3)  artificial cerebrospinal fluid (aCSF) + CV in the same dosis 4) aCSF + CV vehicle was given to the control group. Learning and memory performance were assessed using the passive avoidance task and hole board test. No changes were found in passive avoidance task parameters in any group, although CV reversed the impairment of spatial working memory induced by STZ tested in the hole board. We conclude that STZ 3 mg/kg during two consecutive days did not affect the adquisition and consolidation of long term memory but altered the short term spatial memory. The angiotensin II AT1 receptors are involved in the neurotoxicity effects induced by STZ. The benefic effect of the AT1 blocker could be explained through an increase of the cerebral blood flow (1) and a reduction of the inflammatory effects induced by the neurotoxin (2). 1-Ito, T.; Yamakawa, H.; Bregonzio, C.; Terrón, J.A.; Falcón-neri, A. & Saavedra, J.M. 2002 . Stroke.. 33, 2297-2303 2-Bregonzio, C.; Armando, I.; Ando, H.; Jezova, M.; Baiardi, G. & Saavedra, J.M. 2003. American Journal of Physiology Gastrointestinal and liver physiology.. 285(2):G414-423