AT1 receptors are essential players in the development of amphetamine-induced inflammation in prefrontal cortex: relevance for neuroinflammatory pathologies

MARCHESE, N.A.; OCCHIEPPO. V.B.; BASMADJIAN, O.M.; BREGONZIO, C.

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Neurociencias

Amphetamine (Amph) is related to vascular damage, neuroinflammation, prefrontal cortex (PFC) hypo-function and neuropsychiatric impairments. Angiotensin II, through AT1 receptors (AT1-R), mediates neuroinflammatory responses, promoting endothelial dysfunction, oxidative damage and glial reactivity. The present work aimed to elucidate Amph-induced changes in the cell elements of brain?s innate immune system within the PFC, and to unmask AT1-R? role in its development. Attention deficit was evaluated as a functional assessment of PFC activity. Male Wistar rats (250g) received AT1-R antagonist CV (3mg/kg p.o., days 1?5) and Amph (2.5mg/kg i.p., days 6?10). On day 17, after behavioral tests, brains were processed for cresyl violet staining, GFAP, CD11b and vonWillebrand factor immunohistochemistry. Otherwise, animals exposed to Amph challenge (0.5mg/kg i.p.) were evaluated for oxidative and cellular stresses in isolated brain micro-vessels. Two-way ANOVA and Bonferroni test were used. Amph promoted glial reactivity, apoptosis and vascular network rearrangement in PFC and exacerbated MDA levels and HSP70 expression in response to an Amph challenge in brain micro-vessels. These alterations were observed concomitant with attention deficit. AT1-R blockade prevented the glial reactivity and vascular network rearrangement, the modified micro-vascular responses and the attention deficit induced by Amph, highlighting AT1-R role in the development of Amph-induced neuroinflammation in PFC