Reunión Conjunta SAIC, SAI, SAB, SAP 2019. LXIV Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC)

CONSTANTIN MF; ARTUR DE LA VILLARMOIS, E; CALFA G; MARIELA F PEREZ

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI, SAB, SAP 2019. LXIV Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

SAIC, SAI, SAB, SAP

Sildenafil (SILD) is a drug widely used in clinical practice for its inhibitory effects on phosphodiesterase type 5 (PDE-5), that generate increases in cGMP levels, indirectly enhancing the signaling pathway activated by nitric oxide (NO/GC /GMP). SILD crosses the blood brain barrier, and PDE-5 is expressed in the brain. In the hippocampus (HP), NO increases glutamate release, which is essential for long-term potentiation (LTP) maintenance, a phenomenon of synaptic plasticity that underlies the formation of learning and memory. A acute exposure to SILD improves memory consolidation in mice and previous results from our laboratory showed a facilitation in the generation of LTP in HP 2 hours later, however little is known about the persistence of these changes in that structure and its correlation with learning and memory processes. The objective of the work is to evaluate the effect of SILD on the acquisition of HP-dependent memories and characterize the persistence of the functional and anatomical changes produced in this structure 24 hours, 7 and 30 days after the administration of SILD. For this purpose, male Wistar rats were administered with SILD or saline before training in the "step-down", object recognition test and Y maze, and 4 or 24 hours later the memory acquisition was evaluated. Immediately after the test, 7 or 30 days later, the animals were sacrificed for electrophysiological and neuroanatomic experiments of dendritic spine density. Our results showed that animals administered with SILD have a longer latency time in the step-down test compared to the control group, but a lower rate of exploration of the new object in the object recognition test, while preliminary data on Y maze showed no changes arm discrimination rate compared to control group. On the other hand, SILD improves the synaptic plasticity of HP, reducing the threshold to induce LTP at all times measured, and increases the density of total spines in the HP. These results indicate that SILD would have selective effects on different types of memories, and would induce persistent changes in the functional and structural plasticity of the HP, which temporarily coincide with the effects on memory. It is necessary to carry out new studies on the impact of acute or chronic use of SILD on different types of memories to justify the use of this drug in pathologies related to cognitive deficits.