Subchronic Oral Administration of Benzo[a]pyrene Impairs Motor and Cognitive Behavior and Modulates S100B Levels and MAPKs in Rats

Abstract

Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38(MAPK) and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution.

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

“…Hence, the present study was conducted at PND 5 in male Wistar pups following single intracisternal administration of B[a]P that showed significant increase in spontaneous motor activity at PND 30. The above findings are in agreement with the earlier studies [ 5 ]. Further investigation showed that neonatal 6-OHDA administration leads to spontaneous motor hyperactivity in adolescent rats and the findings are in agreement with previous reports [ 30 ].…”

“…B[a]P induced motor dysfunction leading to spontaneous motor hyperactivity in rodents addresses possible consequences of serious neurological problems [ 5 ]. Several studies have been conducted to show spontaneous motor dysfunction and its association with neurodegenerative symptoms following administration of potent neurotoxicants [ 26 , 27 ].…”

“…The standard experimental paradigm was followed for evaluation of SMA with slight modification [ 5 ]. SMA of rats at PND 30 was individually measured in a home cage with a Supermex system (Muromachi Kikai, Ikeda, Japan).…”

“…Reports also suggest that exposure to B[a]P through early postnatal development leads to impairment in locomotor activity in adolescence [ 4 ]. A recent report revealed that subchronic oral administration of B[a]P in rats leads to spontaneous locomotor hyperactivity [ 5 ]. Behavioral and motor dysfunction following exposure to environmental toxicants like B[a]P is well documented but the neurodegenerative potential of these compounds cannot be ignored.…”

Chronic Administration of Benzo(a)pyrene Induces Memory Impairment and Anxiety-Like Behavior and Increases of NR2B DNA Methylation

“…Moreover, when exposed to high levels, BaP and its metabolites tend to accumulate both in the blood and in the brain [ 7 ], thus causing neurological impairments [ 8 , 9 ]. BaP-induced neurotoxicological effects have been demonstrated in both adult and developing brains, particularly with regard to deficits in long-term spatial memory due to its effects in the hippocampus and prefrontal cortex (PFC) [ 10 – 12 ]. Evidence from human epidemiological studies has also shown that unintended prenatal exposure to BaP adversely affects fetal development, resulting in low birth weight and reduced head circumference, as well as neurobehavioral damage in the offspring [ 13 ].…”