Persistent proteomic changes in glutamatergic and GABAergic signaling in the amygdala of adolescent rats exposed to chlorpyrifos as juveniles.
Persistent proteomic changes in glutamatergic and GABAergic signaling in the amygdala of adolescent rats exposed to chlorpyrifos as juveniles.
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DOI：
10.1016/j.neuro.2021.05.012
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发表时间：
2021-07
期刊：
影响因子：
3.4
通讯作者：
Carr RL
中科院分区：
文献类型：
--
作者：
Alugubelly N;Mohammed AN;Carr RL
毒死蜱（Chlorpyrifos，CPF）是目前使用最广泛的有机磷杀虫剂之一，但其发育神经毒性一直备受关注。暴露于CPF的发育具有长期的负面影响，包括异常的情绪行为。这些负面影响是在接触水平不引起乙酰胆碱酯酶抑制的情况下观察到的，乙酰胆碱酯酶是有机磷农药的典型目标。暴露于这些水平的CPF抑制内源性大麻素代谢酶脂肪酸酰胺水解酶（FAAH），但目前尚不清楚这种抑制的持续影响是什么。为了研究这一点，雄性大鼠幼仔从出生后第10天（PND 10）-PND 16每天经口暴露于玉米油、0.75 mg/kg CPF或0.02 mg/kg PF-04457845（PF; FAAH的特异性抑制剂）。该剂量的CPF不抑制脑胆碱酯酶活性，但抑制FAAH活性。在PND 38（青春期），使用无标记鸟枪蛋白质组学方法测定杏仁核中的蛋白质表达。对照与CPF以及对照与PF的分析分别鉴定出44种和142种差异调节蛋白。基因本体富集分析显示，CPF和PF治疗组中表达改变的蛋白质大多位于突触相关区域，如突触前膜、突触后密度和突触囊泡。两个治疗组影响的不同生物过程包括持续性突触增强、谷氨酸受体信号传导、蛋白磷酸化和化学突触传递。这些结果还表明，谷氨酸能（↓谷氨酸AMPA受体2，↓兴奋性氨基酸转运体2，↑囊泡谷氨酸转运体2）和GABA能信号（↑ GABA转运体3和↑谷氨酸脱羧酶2）之间的平衡失调，这种失衡可能在我们先前报道的异常情绪行为中发挥作用。这些结果表明，CPF和PF之间有类似的表达模式，这两种化学物质可以持续改变情绪行为作为FAAH抑制的结果。
Chlorpyrifos (CPF) remains one of the most widely used organophosphorus insecticides (OPs) despite the concerns about its developmental neurotoxicity. Developmental exposure to CPF has long-lasting negative impacts, including abnormal emotional behaviors. These negative impacts are observed at exposure levels do not cause inhibition of acetylcholinesterase, the canonical target of OPs. Exposure to CPF at these levels inhibits the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) but it is not clear what the persistent effects of this inhibition are. To investigate this, male rat pups were exposed orally to either corn oil, 0.75 mg/kg CPF, or 0.02 mg/kg PF-04457845 (PF; a specific inhibitor of FAAH) daily from postnatal day 10 (PND10) - PND16. This dosage of CPF does not inhibit brain cholinesterase activity but inhibits FAAH activity. On PND38 (adolescence), the protein expression in the amygdala was determined using a label-free shotgun proteomic approach. The analysis of control vs CPF and control vs PF led to the identification of 44 and 142 differentially regulated proteins, respectively. Gene ontology enrichment analysis revealed that most of the proteins with altered expression in both CPF and PF treatment groups were localized in the synapse-related regions, such as presynaptic membrane, postsynaptic density, and synaptic vesicle. The different biological processes affected by both treatment groups included persistent synaptic potentiation, glutamate receptor signaling, protein phosphorylation, and chemical synaptic transmission. These results also indicated disturbances in the balance between glutamatergic (↓ Glutamate AMPA receptor 2, ↓ Excitatory amino acid transporter 2, and ↑ vesicular glutamate transporter 2) and GABAergic signaling (↑ GABA transporter 3 and ↑ glutamate decarboxylast 2).This imbalance could play a role in the abnormal emotional behavior that we have previously reported. These results suggest that there is a similar pattern of expression between CPF and PF, and both these chemicals can persistently alter emotional behavior as a consequence of inhibition of FAAH.
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影响因子：
64.8
作者：
Fu, J;Gaetani, S;Piomelli, D
通讯作者：
Piomelli, D
DOI：
10.1124/jpet.111.180257
发表时间：
2011-07-01
影响因子：
3.5
作者：
Ahn, Kay;Smith, Sarah E.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
DOI：
10.1073/pnas.0903038106
发表时间：
2009-05-12
影响因子：
11.1
作者：
Campolongo, Patrizia;Roozendaal, Benno;Piomelli, Daniele
通讯作者：
Piomelli, Daniele
反复接触毒死蜱会改变抑郁和焦虑动物模型中青春期雄性大鼠的表现
影响因子：
3.4
作者：
Chen, Wen-Qiang;Yuan, Li;Li, Jin
通讯作者：
Li, Jin
过氧化物酶体增殖物激活的受体α在小鼠的行为重复和认知灵活性中起着至关重要的作用。
影响因子：
8.1
作者：
D'Agostino G;Cristiano C;Lyons DJ;Citraro R;Russo E;Avagliano C;Russo R;Raso GM;Meli R;De Sarro G;Heisler LK;Calignano A
通讯作者：
Calignano A