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

Graphical abstract

Schematic diagram for the mechanism B[a]P metabolism by activation that occurs through cytochrome P450 enzymes. During cellular metabolism large amounts of reactive oxygen species (ROS) are generated. The resulting oxidative stress induces the alteration of antioxidant enzymes (GST, GPx, GR and total glutathione) leading towards behavioral changes with altered neuronal morphology in the hippocampus of adult wistar rat brain. Early exposure to B[a]P correlates with impaired learning and memory in adults, and reduction in dendrite population in CA1 regions of hippocampus during development.

Highlights

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  Intraperitoneal B[a]P administration induces anxiolytic like behavior in rats.

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  B[a]P induces oxidative stress and reduces antioxidant enzyme activity.

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  Exposure to B[a]P-induces decrease in dendrite length and spine density through oxidative stress affecting antioxidant defence system.

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  Alteration in the neuronal architecture of the hippocampal cells after B[a]P administration is associated with learning and memory defict.

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.