Reversible alterations in gliar fibrilar acidic protein (Gfap) and tyrosine hydroxylase (TH) expresion after Acute acetaminophen (APAP) intoxication in brain areas involved in locomotion and memory regulation.

GÓMEZ, GIMENA; CAROLINA INÉS GHANEM; VIGO, MARÍA BELÉN; MANAUTOU JE; LAGOS, R

Congreso; Reunión anual de Sociedad Argentina Clínica; 2020

Sociedad Argentina Clínica

We have previously demonstrated that liver toxicity by APAP not resulting in acute organ failure produces hypolocomotion associated with decrease in dopamine levels and reactive astrogliosis in selective brain areas. The aim of the present work was to evaluate if these effects are still present a week after APAP intoxication. For this purpose, male Wistar rats were divided in 4 groups, dosed with APAP (1g/kg; i.p.) or vehicle. After one or seven days of treatment, rats were anesthetized and intracardiacally perfused with PAF. Immunohistochemistry for glial fibrillary acidic protein (Gfap) and tyrosine hydroxylase (TH) expression was performed on free-floating coronal sections. The percentage of reactive area in pre-frontal cortex (Pfc), Nucleus accumbens (NAc), dorsal striatum (DStr) and non-motor cortex (Cx) was quantified using imageJ (NIH). Since control one and seven day treated rats did not show any differences, samples were pooled as a single control group. One day after APAP intoxication, TH expression was decreased in DStr and NACs by 21% [t (2,11)=18.34, p=0.0003] and 20%; [t (2,11)=6.179, p=0.00159], respectively and restored to normal values by 7 days after treatment. However, no significant changes in TH expression were detected in Pfc and Cx at either time point. Moderate reactive astrogliosis was also detected at day one in all dopamine-rich areas of the brain examined, with significant increments in GFAP immunoreactivity by 26% for Pfc [t (2,10)=9.702, p=0.0045]; 88% for DStr [t (2,10)=9.702, p=0.0045] and 25% [t (2,12)=8.156, p=0.0058] for NAc, returning to basal value by day 7. However, no induction of GFAP was detected in Cx and no alterations in astrocyte numbers were observed in any of the areas analyzed at either time point. In conclusion, our results demonstrate that the astrogliosis and altered dopaminergic level are transitory alterations during APAP intoxication in rats and therefore, full recovery in locomotive function is expected.