Neuropeptide Y expression confers benzo[a]pyrene induced anxiolytic like behavioral
response during early adolescence period of male Wistar rats
Saroj Kumar Das, Manorama Patri ⁎
Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India
abstract article info
Article history:
Received 24 May 2016
Received in revised form 4 July 2016
Accepted 4 July 2016
Available online xxxx
Environmental neurotoxicant like benzo[a]pyrene (B[a]P) is known to induce neurobehavioral changes. Our pre-
vious reports address the adverse effect of B[a]P on the neurobehavioral responses and neuromorphology of sen-
sitive brain regions in adolescent rats. Present study was conducted on male Wistar rat neonates at postnatal day
5 (PND5) to ascertain B[a]P induced anxiolytic like behavioral response could be an outcome of neuropeptide Y
(NPY) overexpression in brain. Single intracisternal administration of B[a]P was carried out at PND5 to elucidate
the role of NPY on neurobehavioral responses at PND30. The behavioral studies showed anxiolytic like effect of
B[a]P in both light and dark box and elevated plus maze tests. Antioxidant assay involving glutathione peroxidase
activity was significantly decreased where as lipid peroxidation was significantly augmented in both hippocam-
pus and hypothalamus of B[a]P treated group as compared to naive and control. The neurotransmitter estimation
by HPLC-ECD showed significant increase in 5-HT level in both hippocampus and hypothalamus of B[a]P treated
group. Significant elevation in NPY expression was observed in both hippocampus and hypothalamus of B[a]P
group. Intracellular Ca
2+
estimation using Fura-2AM by fluorometry showed that B[a]P induced increase in
Ca
2+
influx was associated with augmented NPY expression in brain. As NPY has orexigenic effect, our result re-
vealed that there was a significant increase in body weight at PND30 following B[a]P administration to rat neo-
nates at PND5. These findings suggested that NPY overexpression in brain regions might be associated with
anxiolytic like behavioral response and orexigenic effect in rats following single intracisternal B[a]P administra-
tion. Future research directing towards understanding the signaling cascades of B[a]P induced biochemical and
neuromorphological alteration might address the independent pathway which induce neurodegeneration de-
spite NPY overexpression in brain regions of adolescent rats.
© 2016 Published by Elsevier Ltd.
Keywords:
Benzo[a]pyrene
Anxiety
Neuropeptide Y
Calcium
Oxidative stress
Serotonin
1. Introduction
Polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene
(B[a]P) are known for their neurotoxic potential to induce alteration
in behavior, biochemical and neuromorphology of sensitive brain re-
gions (Bouayed et al., 2012; Chen et al., 2012; Mohanty et al., 2016;
Patri et al., 2013; Zhang et al., 2016). B[a]P induced anxiolytic like be-
havioral response has been well documented, but the possible causes
behind this behavioral response are still elusive. B[a]P induced oxidative
stress leading to altered hippocampal cytomorphometry advocates its
neurodegenerative potential (Patel et al., 2016a). Thus the plausible
role of B[a]P in mediating neurodegeneration of sensitive brain regions
can't be ignored (Das et al., 2016a; Patel et al., 2016b).
As neonates are mostly exposed to these neurotoxicants through in-
direct routes such as breast milk and inhaled air over a protracted
period of time, it might exhibit its confounding effects on various organs
of the body including the brain. Most of the prescribed routes of B[a]P
exposure are environmentally relevant, but a direct route of exposure
to study its specific effect on neonatal brain development causing neu-
robehavioral changes during early adolescence period is required.
Intracisternal mode of administration specifically gives a short and di-
rect route to study the effects of B[a]P on neurobehavioral, biochemical,
molecular and neuromorphological changes (Patri et al., 2013; Patel et
al., 2016a). As the blood-brain barrier acts like a check point for meta-
bolic transportation of compounds into the brain tissues, in most of
the previously prescribed route of exposure, it is difficult to measure ap-
proximately the amount of B[a]P injected peripherally that might reach
the brain after crossing liver metabolism. The present approach pro-
vides a unique opportunity to study the effects of B[a]P directly on bio-
chemical status of brain during early stage of postnatal life and to study
behavioral, biochemical and molecular alteration thereof. With the ever
increasing rate of industrialization and growth of human civilization,
exposure to persistent anthropogenic genotoxicants like B[a]P during
early stage of postnatal life might affect the mood status leading to
Neuropeptides xxx (2016) xxx–xxx
⁎ Corresponding author at: Neurobiology Laboratory, Department of Zoology, School of
Life Sciences, Ravenshaw University, Cuttack-753003, Odisha, India.
E-mail address: mpatri@ravenshawuniversity.ac.in (M. Patri).
YNPEP-01732; No of Pages 8
http://dx.doi.org/10.1016/j.npep.2016.07.001
0143-4179/© 2016 Published by Elsevier Ltd.
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Please cite this article as: Das, S.K., Patri, M., Neuropeptide Y expression confers benzo[a]pyrene induced anxiolytic like behavioral response
during early adolescence period of ma..., Neuropeptides (2016), http://dx.doi.org/10.1016/j.npep.2016.07.001