Pascual Rodrigo, Pilar Zamora-León S, Pérez Natalia, Rojas Tatiana, Rojo Anamaría, José Salinas María, Reyes Alvaro, Bustamante Carlos
Laboratorio de Neurociencias, Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Avenida Brasil 2950, Valparaíso, Chile.
Exp Toxicol Pathol. 2011 Jul;63(5):467-71. doi: 10.1016/j.etp.2010.03.006. Epub 2010 Mar 27.
The present study investigated the effects of toluene inhalation and the restorative effects of melatonin on branching and basal dendritic outgrowth of superficial pyramidal neurons in rat's frontal, parietal, and occipital cortices. At postnatal day 21 (P21), Sprague-Dawley male rats were randomly assigned to either an air-only group or a toluene group. From P22 to P32 the animals were exposed to either clean air or toluene vapors (5000-6000 ppm) for 10 min/day. This strategy simulated common toluene abuse in humans, which consists of 15-20 rapid inhalations of highly concentrated solvent. Once the inhalation period was over (P32), toluene exposed animals were randomly reassigned to one of following experimental groups: (i) air-control/saline; (ii) toluene/saline; (iii) toluene/melatonin 0.5mg/kg; (iv) toluene/melatonin 1.0mg/kg; (v) toluene/melatonin 5.0mg/kg; and (vi) toluene/melatonin 10mg/kg. Seven days after the last inhalation (P39), all the animals were sacrificed under deep anesthesia; brains were dissected out and stained according to the Golgi-Cox-Sholl procedure. Layer II/III pyramidal neurons were morphologically analyzed by measuring their basilar dendritic length and the number of branches. The results obtained revealed that (i) toluene inhalation significantly reduced dendritic outgrowth and branching in all cortical areas studied, and (ii) intraperitoneal administration of melatonin (0.5-10mg/kg) was able to restore the dendritic impairment induced by toluene exposure.
本研究调查了吸入甲苯的影响以及褪黑素对大鼠额叶、顶叶和枕叶皮质浅层锥体神经元分支和基底树突生长的恢复作用。在出生后第21天（P21），将Sprague-Dawley雄性大鼠随机分为仅空气组或甲苯组。从P22到P32，动物每天暴露于清洁空气或甲苯蒸气（5000 - 6000 ppm）中10分钟。这种策略模拟了人类常见的甲苯滥用情况，即快速吸入15 - 20次高浓度溶剂。一旦吸入期结束（P32），暴露于甲苯的动物被随机重新分配到以下实验组之一：（i）空气对照/生理盐水组；（ii）甲苯/生理盐水组；（iii）甲苯/0.5mg/kg褪黑素组；（iv）甲苯/1.0mg/kg褪黑素组；（v）甲苯/5.0mg/kg褪黑素组；（vi）甲苯/10mg/kg褪黑素组。在最后一次吸入后7天（P39），所有动物在深度麻醉下处死；取出大脑并按照高尔基-考克斯-肖尔程序进行染色。通过测量其基底树突长度和分支数量对II/III层锥体神经元进行形态学分析。获得的结果表明：（i）吸入甲苯显著减少了所有研究皮质区域的树突生长和分支；（ii）腹腔注射褪黑素（0.5 - 10mg/kg）能够恢复由甲苯暴露引起的树突损伤。
