AT1 Receptors Are Essential Players in the Development of AmphetamineInduced Inflammation in Prefrontal Cortex: Relevance for Neuroinflammatory Pathologies

MARCHESE NATALIA A.; OCCHIEPPO VICTORIA B; BASMADJIAN OSVALDO M; BREGONZIO CLAUDIA

Córdoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Sociedad Argentina en investigación en neurociencias (SAN)

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 the brain?sinnate immune system within the PFC and to unmask AT1-R?s role in its development. Attention deficit was evaluated as a functional assessment of PFC activity. Male Wistar rats (250 g) received AT1-R antagonist CV (3 mg/kg p.o.,Days 1?5) and Amph (2.5 mg/kg i.p., Days 6?10). On Day 17, after behavioral tests, brains were processed for cresyl violet staining, GFAP, CD11b, and von Willebrand factor immunohistochemistry. Otherwise, animals exposed to Amph challenge (0.5 mg/kg i.p.) were evaluated for oxidative and cellular stresses in isolated brain microvessels. 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 microvessels. 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.