Patel Dhyanesh Arvind, Booze Rosemarie M, Mactutus Charles F
University of South Carolina, Columbia, SC 29208, USA.
Int J Dev Neurosci. 2012 Feb;30(1):1-9. doi: 10.1016/j.ijdevneu.2011.11.001. Epub 2011 Nov 17.
Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP(+) (type B cells) and nestin(+)(GFAP(-)) (type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP(+) expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP(+) expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin(+) expression with females showing approximately 8-13% higher nestin(+) expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin(+) expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females.
早期发育阶段接触滥用药物的长期后果可能会对大脑的增殖可塑性产生有害影响。本研究的目的是使用静脉注射途径和模仿人类可卡因使用时动脉峰值水平的剂量，来研究产前接触可卡因对成年（180日龄）大鼠脑室下区（SVZ）增殖细胞类型的长期影响。采用免疫细胞化学方法，对SVZ胼胝体下区域中GFAP(+)（B型细胞）和巢蛋白(+)（GFAP(-)）（C型和A型细胞）染色的表达进行定量分析。产前可卡因处理组和载体（生理盐水）对照组之间的GFAP(+)表达存在显著差异。与载体对照组相比，产前可卡因处理组的GFAP(+)表达显著降低，这表明产前接触可卡因显著降低了SVZ中B型神经干细胞的表达。此外，巢蛋白(+)表达存在显著的性别差异，雌性的巢蛋白(+)表达比雄性高约8 - 13%。更重要的是，证实了巢蛋白(+)表达存在显著的产前处理条件（产前可卡因、对照）与性别的交互作用，表明可卡因对动物性别的影响不同。具体而言，产前接触可卡因消除了两性之间的基础差异。总的来说，目前的研究结果表明，当通过旨在捕捉娱乐性使用突出特征的方案给予产前可卡因时，它可以选择性地改变成年大鼠大脑SVZ胼胝体下区域的主要增殖细胞类型，并且对雄性和雌性的影响不同。
