Sex differences in effects of low level domoic acid exposure
Sex differences in effects of low level domoic acid exposure
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DOI：
10.1016/j.neuro.2012.10.010
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发表时间：
2013-01-01
期刊：
影响因子：
3.4
通讯作者：
Judge, Sarah J.
中科院分区：
文献类型：
--
作者：
Baron, Andrew W.;Rushton, Steven P.;Judge, Sarah J.
食用含有植物毒素软骨藻酸（DOM）的海产品会导致人类和动物的神经毒性。据报道，DOM引起的症状可能在男性中比女性更严重，但迄今为止，性别对DOM引起的成人效应的影响尚不清楚。我们研究了成年大鼠DOM诱导效应的性别差异。由于低水平暴露对人类健康的影响最大（由于DOM监管限制），我们研究了低水平暴露的影响。成年雄性和雌性Sprague道利大鼠单次腹腔注射DOM（0、1.0、1.8 mg/kg）。行为监测3小时，背海马和嗅球的免疫组化也进行了检查。DOM增加运动和梳理活动，与车辆组相比。DOM暴露也显着增加刻板行为和磷酸化cAMP反应元件结合蛋白（pCREB-IR）的免疫反应性下降。性别对行为反应的大小没有影响，但DOM诱导的自发活动和耳部抓挠的发生在女性中比男性更快。混合效应模型显示，在运动活动响应DOM的预测峰值也更快，在女性比男性。2/7只雄性大鼠和0/8只雌性大鼠接受1.8 mg/kg DOM给药后出现严重毒性。这些数据表明，暴露于低水平DOM的男性可能更容易受到严重的神经毒性，而女性更快地受到影响。了解DOM诱导的神经毒性的性别差异可能有助于未来的保护策略和治疗。(c)2012 Elsevier Inc. All rights reserved.
Consumption of seafood containing the phytoplankton-derived toxin domoic acid (DOM) causes neurotoxicity in humans and in animals. It has been reported that DOM-induced symptoms may be more severe in men than women, but to date the effect of sex on DOM-induced effects in adults is not known. We investigated sex differences in DOM-induced effects in adult rats. Since low level exposure is of greatest relevance to human health (due to DOM regulatory limit), we examined the effects of low level exposure. Adult male and female Sprague Dawley rats were administered a single intraperitoneal injection of DOM (0, 1.0, 1.8 mg/kg). Behaviour was monitored for 3 h and immunohistochemistry in the dorsal hippocampus and olfactory bulb was also examined. DOM increased locomotor and grooming activity, compared to vehicle group. DOM exposure also significantly increased stereotypic behaviours and decreased phosphorylated cAMP response element-binding protein immunoreactivity (pCREB-IR). There was no effect of sex on the magnitude of the behavioural responses, but the onset of DOM-induced locomotor activity and ear scratches was quicker in females than in males. Mixed effect modelling revealed the predicted peak in locomotor activity in response to DOM was also quicker in females than in males. Severe toxicity was evident in 2/7 male rats and 0/8 female rats dosed with 1.8 mg/kg DOM. These data suggest that males exposed to low level DOM may be more susceptible to severe neurotoxicity, whereas females are affected more quickly. Understanding sex differences in DOM-induced neurotoxicity may contribute to future protective strategies and treatments. (c) 2012 Elsevier Inc. All rights reserved.