AT1 receptors of angiotensin ii induce working memory deficit associated with transient angiogenesis, peroxidation and gliosis in prelimbic prefrontal cortex after amphetamine exposure

BASMADJIAN, OSVALDO MARTIN; ARMONELLI, SAMANTA; MARCHESE, NATALIA ANDREA; BAIARDI, GUSTAVO; OCCHIEPPO, VICTORIA BELÉN; BREGONZIO, CLAUDIA

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Congreso; The 21 International Vascular Biology Meeting; 2020

International Vascular Biology Meeting 2020

Microvessels, astrocytes, microglia and neurons constitute the neurovascular unit. This functional coupling allows vessels to adequately satisfy metabolic demands of neurons. Consequently, a dysfunction of neurovascular unit will result in brain function alterations. Moreover, it is well know that amphetamine exposure induces reactivity changes over microglial cell, astrocytes and vascular changes. On the other hand, AT1 receptors of angiotensin II are present over all of neurovascular unit components.This work aimed to study AT1 receptors involvement in working memory deficit and neurovascular unit alteration over prelimbic prefrontal cortex after amphetamine exposure. Male Wistar rats (250-300g) were used. To study the participation of AT1-R in amphetamine effects, the AT1-R blocker Candesartan (CV 3mg/kg p.o.) was administered for 10 days and Amphetamine (2.5 mg/kg i.p.) was daily administred from day 6 to 10. On week 1 and 3 of Amph withdrawal, working memory was evaluated using Y-maze test. 24h later, the animals were perfused and the brains prepared for GFAP, CD11b and von Willebrand immunohistochemistry to evaluate astrogliosis, microgliosis and agiogenesis respectively. The results were analyzed using 2-way ANOVA followed by Bonferroni test.It was found that repeated amphetamine exposure induce working memory deficit together with gliosis at week 1 and 3 over prelimbic prefrontal cortex. All of these alterations were prevented with the AT1 receptor blockade. Amphetamine exposure induced angiogenesis at week 1 that retracted at week 3. We conclude that AT1 receptors participate in amphetamine-induced neurovascular alterations that alter prelimbic prefrontal cortex function observed as working memory deficit.