Early Postnatal Benzo(a)pyrene Exposure in Sprague-Dawley Rats Causes Persistent Neurobehavioral Impairments that Emerge Postnatally and Continue into Adolescence and Adulthood

Abstract

Previous studies have demonstrated that benzo(a)pyrene (BaP) may disrupt the development of key biological systems, thus leaving children more vulnerable to functional impairments in adulthood. The current study was conducted to determine whether neurotoxic effects of postnatal BaP exposure on behavioral performance persist in juvenile and young adult stages. Therefore, neonate Sprague-Dawley pups were given oral doses of BaP (0.02, 0.2, and 2 mg/kg/day) continuing through a period of rapid brain development (on postnatal days [PNDs] 5-11). Further, developmental milestones and behavioral endpoints assessing sensory and motor maturation were examined. Also, in this study, Morris water maze and elevated plus maze were used for evaluating the cognitive function and anxiety-like behavior. Our results showed that there was altered ontogeny in a few measures of neuromotor development; however, other developmental milestones and sensory responses were not altered significantly. Moreover, the locomotor activity deficit in BaP-treated pups was evident at PND 36 and was most pronounced in the PND 69. Also, exposure to BaP during early postnatal development had an adverse effect on adult rats (PND 70) in the elevated plus maze, and the swim maze suggests that low doses of BaP impair spatial learning functions at adult test period. In contrast, BaP exposure had no evident effect on behaviors in these two mazes for adolescent animals. These data clearly indicate that behavioral impairments resulting from postnatal BaP exposure are potentially long-lasting and may not be apparent in juveniles, but are present in young adulthood.

Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats

“…Exposure to B[a]P during early postnatal life of rats led to neurobehavioural impairment during adolescence [39]. However, the present work demonstrated that intracisternal B[a]P exposure during neonatal brain development may lead to production of reactive oxygen species causing oxidative stress and DNA damage during the early adolescence period of rats.…”

“…Environmental monitoring studies reported PAH levels in the range of 0.1-10 µg/m 3 in rural houses of developing countries as compared to 0.02-0.1 µg/m 3 in traffic and 20-100 ng/cigarette [40,41]. In most of the studies, exposure to these environmental pollutants was carried out at concentrations consistent with environmental levels or far above the limit [39,42,43]. Studies have also shown that lactational exposure to low doses of B[a]P (2 and 20 mg/kg BW) during early postnatal development adversely affects neurobehavioural responses in later phases of life [44].…”

Adverse effect of sub-chronic exposure to benzo(a)pyrene and protective effect of butylated hydroxyanisole on learning and memory ability in male Sprague-Dawley rat

“…(Morris et al, 1982;Morris, 1984). The studies of exposure to B(a)P showed that neuronal damage was found in the hippocampus, spatial learning and memory deficits associated protein expression signatures (Chen et al, 2012). Behavior was the most significantly affected gene ontology category and learning and memory ranked fourth (Qiu et al, 2011).…”

Effects of benzo(a)pyrene exposure on the atpase activity and calcium concentration in the hippocampus of neonatal rats

“…Thus, B(a)P exposure may have an advanced impact on the central nervous system (CNS) [4]. Besides its carcinogenicity, some studies have also revealed that B(a)P has neurobehavioral toxicity [5,6]. A number of epidemiological studies have shown that children may be more sensitive to neurological poison because of their immature nervous system.…”

“…A number of epidemiological studies have shown that children may be more sensitive to neurological poison because of their immature nervous system. Several experimental studies have further revealed that B(a)P could cause the deficits in the process of cognitive development in the infant Sprague Dawley (SD) rats and thus inducing neural impairment [6,7]. Moreover, the gestational exposure to B(a)P may affect the neural development and lead to cognitive decline [3,8].…”