Martyniuk Christopher J, Sanchez Brian C, Szabo Nancy J, Denslow Nancy D, Sepúlveda Maria S
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA.
Aquat Toxicol. 2009 Oct 19;95(1):1-9. doi: 10.1016/j.aquatox.2009.06.009. Epub 2009 Jun 21.
Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens (microg/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl(2)) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 microg/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 microg/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 microg/g) but increased cGnRH-II mRNA at the lowest dose (5 microg/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.
许多水生污染物都可能影响中枢神经系统,然而,有毒物质如何改变正常脑功能的潜在机制尚未得到充分了解。本研究的目的是比较新兴和常见环境污染物对在神经递质合成和繁殖中起作用的脑转录本表达的影响。成年雄性大口黑鲈(Micropterus salmoides)单次注射,持续96小时,注射物为对照物(水或油)或两种剂量之一的单一化学物质,以达到以下体内负荷(微克/克):阿特拉津(0.3和3.0)、毒杀芬(10和100)、镉(CdCl₂)(0.000067和0.00067)、多氯联苯(PCB)126(0.25和2.5)以及菲(5和50)。克隆了大口黑鲈参与神经递质(谷氨酸脱羧酶65,GAD65;酪氨酸羟化酶)和雌激素(脑芳香化酶;CYP19b)合成的酶的部分基因片段,用于实时PCR分析。此外,还研究了调节摄食(神经肽Y)和繁殖(鸡促性腺激素释放激素II,cGnRH-II;鲑鱼促性腺激素释放激素,sGnRH)的神经肽。在所测试的化学物质中,只有镉、PCB 126和菲对所测试的基因有显著影响,而阿特拉津和毒杀芬则没有。镉(0.000067微克/克)显著增加cGnRH-II mRNA水平,而PCB 126(0.25微克/克)降低GAD65 mRNA水平。菲在最高剂量(50微克/克)时降低GAD65和酪氨酸羟化酶mRNA水平,但在最低剂量(5微克/克)时增加cGnRH-II mRNA水平。CYP19b、NPY和sGnRH mRNA水平不受任何处理的影响。就所测试的基因而言,层次聚类树状图将PCB 126和菲聚在一起的程度比其他化学物质更为紧密。本研究表明,对神经递质合成和神经内分泌功能重要的脑转录本是新兴和常见水生污染物的潜在作用靶点。