Patel Bhupesh, Das Saroj Kumar, Das Swagatika, Das Lipsa, Patri Manorama
Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India.
Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India; Defence Institute of High Altitude Research, DRDO, Jammu and Kashmir, India.
Int J Dev Neurosci. 2016 May;50:7-15. doi: 10.1016/j.ijdevneu.2016.01.006. Epub 2016 Mar 2.
Environmental neurotoxicants like benzo[a]pyrene (B[a]P) have been well documented regarding their potential to induce oxidative stress. However, neonatal exposure to B[a]P and its subsequent effect on anti-oxidant defence system and hippocampal cytomorphometry leading to behavioral changes have not been fully elucidated. We investigated the effect of acute exposure of B[a]P on five days old male Wistar pups administered with single dose of B[a]P (0.2 μg/kg BW) through intracisternal mode. Control group was administered with vehicle i.e., DMSO and a separate group of rats without any treatment was taken as naive group. Behavioral analysis showed anxiolytic-like behavior with significant increase in time spent in open arm in elevated plus maze. Further, significant reduction in fall off time during rotarod test showing B[a]P induced locomotor hyperactivity and impaired motor co-ordination in adolescent rats. B[a]P induced behavioral changes were further associated with altered anti-oxidant defence system involving significant reduction in the total ATPase, Na(+) K(+) ATPase, Mg(2+) ATPase, GR and GPx activity with a significant elevation in the activity of catalase and GST as compared to naive and control groups. Cytomorphometry of hippocampus showed that the number of neurons and glia in B[a]P treated group were significantly reduced as compared to naive and control. Subsequent observation showed that the area and perimeter of hippocampus, hippocampal neurons and neuronal nucleus were significantly reduced in B[a]P treated group as compared to naive and control. The findings of the present study suggest that the alteration in hippocampal cytomorphometry and neuronal population associated with impaired antioxidant signaling and mood in B[a]P treated group could be an outcome of neuromorphological alteration leading to pyknotic cell death or impaired differential migration of neurons during early postnatal brain development.
像苯并[a]芘（B[a]P）这样的环境神经毒素，其诱导氧化应激的潜力已有充分记录。然而，新生期接触B[a]P及其随后对抗氧化防御系统和海马细胞形态计量学的影响导致行为改变，尚未完全阐明。我们研究了通过脑池内给药方式，对5日龄雄性Wistar幼崽单次给予B[a]P（0.2μg/kg体重）后急性暴露于B[a]P的影响。对照组给予溶剂即二甲亚砜（DMSO），另一组未经任何处理的大鼠作为未处理组。行为分析显示，在高架十字迷宫中，B[a]P处理组出现抗焦虑样行为，在开放臂停留时间显著增加。此外，在转棒试验中，B[a]P处理组的跌落时间显著缩短，表明B[a]P诱导青春期大鼠运动亢进和运动协调受损。与未处理组和对照组相比，B[a]P诱导的行为改变还与抗氧化防御系统改变有关，包括总ATP酶、钠钾ATP酶、镁ATP酶、谷胱甘肽还原酶（GR）和谷胱甘肽过氧化物酶（GPx）活性显著降低，而过氧化氢酶和谷胱甘肽S-转移酶（GST）活性显著升高。海马细胞形态计量学显示，与未处理组和对照组相比，B[a]P处理组的神经元和神经胶质细胞数量显著减少。随后的观察表明，与未处理组和对照组相比，B[a]P处理组海马、海马神经元和神经元细胞核的面积和周长显著减小。本研究结果表明，B[a]P处理组海马细胞形态计量学和神经元数量的改变与抗氧化信号传导受损和情绪变化相关，可能是神经形态学改变导致核固缩细胞死亡或出生后早期脑发育过程中神经元迁移分化受损的结果。
