Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 Cape Town, South Africa.
Metab Brain Dis. 2012 Sep;27(3):363-75. doi: 10.1007/s11011-012-9295-9. Epub 2012 Mar 28.
Early life adversity has been suggested to predispose an individual to later drug abuse. The core and shell sub-regions of the nucleus accumbens are differentially affected by both stressors and methamphetamine. This study aimed to characterize and quantify methamphetamine-induced protein expression in the shell and core of the nucleus accumbens in animals exposed to maternal separation during early development. Isobaric tagging (iTRAQ) which enables simultaneous identification and quantification of peptides with tandem mass spectrometry (MS/MS) was used. We found that maternal separation altered more proteins involved in structure and redox regulation in the shell than in the core of the nucleus accumbens, and that maternal separation and methamphetamine had differential effects on signaling proteins in the shell and core. Compared to maternal separation or methamphetamine alone, the maternal separation/methamphetamine combination altered more proteins involved in energy metabolism, redox regulatory processes and neurotrophic proteins. Methamphetamine treatment of rats subjected to maternal separation caused a reduction of cytoskeletal proteins in the shell and altered cytoskeletal, signaling, energy metabolism and redox proteins in the core. Comparison of maternal separation/methamphetamine to methamphetamine alone resulted in decreased cytoskeletal proteins in both the shell and core and increased neurotrophic proteins in the core. This study confirms that both early life stress and methamphetamine differentially affect the shell and core of the nucleus accumbens and demonstrates that the combination of early life adversity and later methamphetamine use results in more proteins being affected in the nucleus accumbens than either treatment alone.
早期生活逆境被认为使个体易患后期药物滥用。伏隔核的核心和壳区亚区受到应激源和甲基苯丙胺的不同影响。本研究旨在描述和量化在早期发育过程中经历母体分离的动物中，甲基苯丙胺对伏隔核壳区和核区蛋白表达的影响。同位素质谱标记（iTRAQ）可用于串联质谱（MS/MS）同时鉴定和定量肽。我们发现，母体分离改变了更多涉及壳区结构和氧化还原调节的蛋白质，而不是核区，母体分离和甲基苯丙胺对壳区和核区的信号蛋白有不同的影响。与母体分离或甲基苯丙胺单独作用相比，母体分离/甲基苯丙胺联合作用改变了更多涉及能量代谢、氧化还原调节过程和神经营养蛋白的蛋白质。母体分离的大鼠给予甲基苯丙胺处理导致壳区细胞骨架蛋白减少，并改变核区的细胞骨架、信号、能量代谢和氧化还原蛋白。将母体分离/甲基苯丙胺与甲基苯丙胺单独比较，导致壳区和核区的细胞骨架蛋白减少，核区的神经营养蛋白增加。本研究证实，早期生活应激和甲基苯丙胺均能使伏隔核的壳区和核区产生差异，并表明早期生活逆境和后期使用甲基苯丙胺的联合作用导致伏隔核中受影响的蛋白质比单独处理更多。
