Developmental deltamethrin: Sex-specific hippocampal effects in Sprague Dawley rats

IF 2.9 Q2 TOXICOLOGY
Emily M. Pitzer , Chiho Sugimoto , Samantha L. Regan , Gary A. Gudelsky , Michael T. Williams , Charles V. Vorhees
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Abstract

Pyrethroid pesticides are widely used and can cause long-term effects after early exposure. Epidemiological and animal studies reveal associations between pyrethroid exposure and altered cognition following prenatal and/or neonatal exposure. However, little is known about the cellular effects of such exposure. Sprague Dawley rats were gavaged with 0 or 1.0 mg/kg deltamethrin (DLM), a Type II pyrethroid, in corn oil (dose volume 5 mL/kg) once per day from postnatal day (P) 3–20 and assessed shortly after dosing ended or as adults. No effects of DLM exposure were found on striatal dopaminergic markers, nor on AMPA receptor subunits or on NMDA-NR1. However, DLM increased NMDA-NR2A and decreased NMDA-NR2B levels in the hippocampus, in males but not females. Additionally, adult hippocampal CA1 long-term potentiation was increased in DLM-treated males but not females. Potassium stimulated extracellular glutamate release in the hippocampus was not affected using in vivo microdialysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed increased apoptotic cells in the dentate gyrus of male rats, in the absence of changes in cleaved caspase-3 at P21. Proinflammatory cytokines interferon gamma trended up in striatum, interleukin-1β trended down in nucleus accumbens, IL-13 trended up in hippocampus, and keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO or CXCL1) was significantly increased in the hippocampus in male DLM-treated rats on P20. The data point to the developing hippocampus as a susceptible region to DLM-induced adverse effects.

Abstract Image

发育型溴氰菊酯:Sprague Dawley大鼠性别特异性海马效应
拟除虫菊酯类杀虫剂被广泛使用,早期接触后会造成长期影响。流行病学和动物研究表明,在产前和/或新生儿接触拟除虫菊酯与认知改变之间存在关联。然而,人们对这种暴露对细胞的影响知之甚少。从出生后3-20日起,每天1次在玉米油中灌胃0或1.0 mg/kg溴氰菊酯(DLM,一种II型拟除虫菊酯)(剂量体积为5 mL/kg),并在给药结束后不久或成年后进行评估。DLM暴露对纹状体多巴胺能标志物、AMPA受体亚基或NMDA-NR1均无影响。然而,DLM在雄性海马中增加了NMDA-NR2A水平,降低了NMDA-NR2B水平,而在雌性海马中没有。此外,成年海马CA1长期增强在dlm治疗的男性中增加,而在女性中没有。体内微透析不影响钾刺激海马细胞外谷氨酸释放。末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)显示雄性大鼠齿状回中凋亡细胞增加,而P21位点的cleaved caspase-3没有变化。P20时,雄性dlm治疗大鼠纹状体促炎因子干扰素γ呈上升趋势,伏隔核白介素-1β呈下降趋势,海马IL-13呈上升趋势,海马角化细胞趋化因子/人生长调节癌基因(KC/GRO或CXCL1)显著升高。数据表明,发育中的海马体是易受dlm诱导的不良反应影响的区域。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Research in Toxicology
Current Research in Toxicology Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
4.70
自引率
3.00%
发文量
33
审稿时长
82 days
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