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对鱼类杀藻菌对幼年和成年大鼠影响的快速神经行为分析

Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats.

作者信息

Levin E D, Rezvani A H, Christopher N C, Glasgow H B, Deamer-Melia N J, Burkholder J M, Moser V C, Jensen K

机构信息

Department of Psychiatry, Duke University Medical Center, Duke University, Durham, NC 27710, USA.

出版信息

Neurotoxicol Teratol. 2000 Jul-Aug;22(4):533-40. doi: 10.1016/s0892-0362(00)00080-5.

Abstract

The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague-Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group (N = 12) was injected with saline and one (N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples (p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the juvenile rats. Furthermore, there were no differences between male and female rats in the Pfiesteria-induced choice accuracy impairment. Pfiesteria effects on choice accuracy in the radial-arm maze in rats constitute a critical component of the model of Pfiesteria toxicity, because the hallmark of Pfiesteria toxicity in humans is cognitive dysfunction. Our finding that analysis of the first six sessions of radial-arm maze testing is sufficient for determining the effect means that this test will be useful as a rapid screen for identifying the critical neurotoxin(s) of Pfiesteria in future studies.

摘要

河口甲藻杀鱼费氏藻已知会杀死鱼类,并与人类的神经认知缺陷有关。我们已经建立了一个大鼠模型来证明接触费氏藻会导致显著的学习障碍。这在放射状臂迷宫学习过程中反复表现为选择准确性受损。在“8”字形装置的运动活动测试中也观察到了费氏藻诱导的效应。目前的研究使用短期放射状臂迷宫获取、“8”字形活动测试和功能性观察量表(FOB)来评估费氏藻对成年和幼年大鼠的神经行为影响。在研究1中,评估了三种不同费氏藻培养物(Pf 113、Pf 728和Pf Vandermere)的神经行为效力。96只(每组12只)成年雌性斯普拉格-道利大鼠皮下注射单剂量取自水族箱培养的费氏藻(每千克大鼠体重35600或106800个费氏藻细胞)。一个对照组(N = 12)注射生理盐水,另一个对照组(N = 12)注射不含费氏藻的水族箱水。所有三种费氏藻样本(p < 0.05)在训练的前六个阶段均损害了选择准确性。在放射状臂迷宫选择准确性受损时,使用FOB未观察到明显的与费氏藻相关的效应,这表明费氏藻诱导的选择准确性缺陷不是由于全身虚弱所致。在“8”字形装置中,费氏藻处理导致平均运动活动显著降低。在研究2中,评估了Pf 728样本类型对幼年大鼠的神经行为影响。24日龄的雄性和雌性大鼠每千克体重注射3560个或10680个Pf - 728费氏藻细胞。与成年雌性大鼠一样,幼年大鼠在放射状臂迷宫选择准确性方面表现出显著受损。在幼年大鼠中未检测到运动活动或FOB的变化。此外,在费氏藻诱导的选择准确性受损方面,雄性和雌性大鼠之间没有差异。费氏藻对大鼠放射状臂迷宫选择准确性的影响是费氏藻毒性模型的关键组成部分,因为费氏藻对人类毒性的标志是认知功能障碍。我们的发现,即对放射状臂迷宫测试的前六个阶段进行分析足以确定效应,意味着该测试在未来研究中作为快速筛选以鉴定费氏藻关键神经毒素将是有用的。

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