Organochlorine pesticide effects on neurotransmitter signaling

有机氯农药对神经递质信号传导的影响

• 批准号: 7661803
• 负责人: Christopher Joseph Martyniuk
• 金额: $ 4.72万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-11-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7661803
• 关键词: Affect; Animals; Apical; Apoptosis; Bass; Biochemical; Bioinformatics; Biological Assay; Biological Markers; Brain; Cell Death; Data; Dieldrin; Dopamine; Endosulfan; Environment; Environmental Exposure; Environmental Pollution; Enzymes; Epidemiology; Estrogens; Event; Exposure to; Florida; GABA-A Receptor; Gene Proteins; Genomics; Goals; Gonadal Steroid Hormones; Gonadal structure; Gonadotropins; Health; Human; Hypothalamic structure; Lead; Link; Measures; Mentors; Messenger RNA; Metabolism; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurosecretory Systems; Neurotransmitters; Pathway interactions; Pesticides; Phase; Physiological; Pituitary Gland; Pituitary Gonadotropins; Production; Proteins; Proteomics; Receptor Inhibition; Receptor Signaling; Regulation; Reproduction; Research; Research Personnel; Risk; Role; Signal Transduction; Steroids; Stress; System; Systems Biology; Time; Toxicogenomics; Toxicology; Training; Universities; Vertebrates; Water; Wound Healing; enzyme activity; feeding; gamma-Aminobutyric Acid; hypothalamic pituitary gonadal axis; mature animal; mind control; neurochemistry; neurophysiology; neurotransmission; neurotransmitter metabolism; organochlorine pesticide; organochlorine pesticide exposure; pesticide exposure; programs; receptor; receptor function; reproductive; research study; response; retinal rods; sex; tool

DESCRIPTION (provided by applicant) The candidate current postdoctoral research at the University of Florida (UF) is studying the response of proteins to environmental contaminants and is an excellent compliment to his neurogenomics and neurophysiology background. The candidate chose UF for his postdoctoral research and mentored research because UF has a well established research center (ICBR) dedicated to genomic and proteomic analysis and the Center for Environmental and Human Toxicology has a strong toxicogenomic research program. His long term research goals are to develop the tools needed to study the effects of environmental contaminants on neuroendocrine function and impacts on the vertebrate HPG axis. This proposal investigates the effects of organochloride pesticides (OCRs) dieldrin and alpha-endosulfan on neuroendocrine function and the regulation of reproduction. These OCRs are persistent in the environment and continue to be a concern for wildlife and human health. Major targets of OCR exposure are the neurotransmitters GABA (GABA-A receptors) and dopamine (DA). During the mentored phase, the candidate's immediate goals will be continued training in proteomics. This is a growing field that will compliment his strong background in genomics to understand molecular events underlying neurophysiology. He will also adapt bioinformatic approaches to integrate physiological, genomic, and proteomic data. In the independent research phase, the candidate will study the effects of OCRs on GABA and DA metabolizing enzyme abundance and activity since there is evidence that enzyme activity is altered with neurodegenerative diseases. He will use morphological (apoptosis) and biochemical endpoints in the brain (neurotransmitter metabolism and levels), pituitary (gonadotropin synthesis), and gonad (steroid production) as phenotypic anchors for genomic (microarray) and proteomic (iTRAQ) to better understand how OCRs impact the brain and the control of reproduction. This systems biology approach can be utilized to study other neuroactive compounds in the environment to assess risks to environmental and human health.

描述（由申请人提供） 候选人目前在佛罗里达大学（UF）的博士后研究正在研究蛋白质对环境污染物的反应，这是对他的神经基因组学和神经生理学背景的一个很好的补充。候选人选择UF为他的博士后研究和指导研究，因为UF有一个完善的研究中心（ICBR）致力于基因组和蛋白质组学分析和环境与人类毒理学中心有一个强大的毒理基因组学研究计划。 他的长期研究目标是开发研究环境污染物对神经内分泌功能的影响以及对脊椎动物HPG轴的影响所需的工具。本提案调查了有机氯农药、狄氏剂和甲型硫丹对神经内分泌功能和生殖调节的影响。这些有机氯化合物在环境中具有持久性，并继续成为野生动物和人类健康的一个问题。 OCR暴露的主要目标是神经递质GABA（GABA-A受体）和多巴胺（DA）。 在指导阶段，候选人的直接目标将是继续蛋白质组学培训。这是一个不断发展的领域，将补充他在基因组学方面的强大背景，以了解神经生理学基础的分子事件。 他还将采用生物信息学方法来整合生理，基因组和蛋白质组数据。 在独立研究阶段，候选人将研究OCR对GABA和DA代谢酶丰度和活性的影响，因为有证据表明酶活性随着神经退行性疾病而改变。 他将使用形态学（细胞凋亡）和脑（神经递质代谢和水平），垂体（促性腺激素合成）和性腺（类固醇产生）的生化终点作为基因组（微阵列）和蛋白质组学（iTRAQ）的表型锚，以更好地了解OCR如何影响大脑和生殖控制。这种系统生物学方法可用于研究环境中的其他神经活性化合物，以评估对环境和人类健康的风险。

项目成果

Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides).

• DOI: 10.1016/j.ygcen.2014.03.029
• 发表时间: 2014-07-01
• 期刊: GENERAL AND COMPARATIVE ENDOCRINOLOGY
• 影响因子: 2.7
• 作者: Richter, Catherine A.;Martyniuk, Christopher J.;Annis, Mandy L.;Brumbaugh, William G.;Chasar, Lia C.;Denslow, Nancy D.;Tillitt, Donald E.
• 通讯作者: Tillitt, Donald E.

Are we forgetting the "proteomics" in multi-omics ecotoxicology?

• DOI: 10.1016/j.cbd.2020.100751
• 发表时间: 2020-10
• 期刊: Comparative biochemistry and physiology. Part D, Genomics & proteomics
• 作者: Xuefang Liang;C. Martyniuk;D. Simmons