Adolescence benzo[a]pyrene treatment induces learning and memory impairment and anxiolytic like behavioral response altering neuronal morphology of hippocampus in adult male Wistar rats

Abstract

Exposure to benzo[a]pyrene (B[a]P), a prototype of polycyclic aromatic hydrocarbons (PAHs) easily cross blood brain barrier (BBB) and is associated with impaired learning and memory in adult rats. However, there is no symmetric study reported on association between B[a]P exposure during the early development and hippocampal dendritic architecture causing behavioral changes like learning and memory deficit of adult rats. We investigated a fourteen day consecutive B[a]P administration, intraperitonial (i.p.), with two different doses (0.1 and 1μM) during early adolescence at PND30-44 and learning behavior assessed between PND 45-60 in adult male rats. The anxiolytic like behavioural analysis was done by LDPT. Depressive like behaviour was estimated through sucrose preference and learning and memory by T-maze. After B[a]P administration oxidative stress markers like glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), reduced (GSH) and oxidized glutathione (GSSG) were evaluated. To parallel these behavioral and antioxidant level changes to alteration in dendritic morphology, Golgi-Cox staining was performed in the hippocampus. Our study showed anxiolytic like behavioral response with significant increase in time spent in light zone and significant (p < 0.05) decrease in preference for sucrose and a reduction in percentage of spontaneous responses in T-maze test in B[a]P administered group as compared to vehicle control. B[a]P exposed male rats showed significant increase in GST activity (p < 0.05) and concentration of GSSG with a decay in GSH, GPx and GR in both the groups as compared to control. B[a]P administered rats showed significant loss in total dendritic length and number (28%) with reduced spine density (18%) in both higher and lower doses. These results suggested that B[a]P administration can be associated with an increase ROS production showing altered antioxidant defence system through glutathione biosynthesis and causing profound alterations in dendritic length and spine density of hippocampal neurons leading towards learning and memory deficits in adult rats. Keywords: PAHs, ROS, Oxidative stress, Antioxidant enzymes, Anxiolytic like behavior, Depression, Learning and memory