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体内甲基汞暴露可在大鼠皮质切片的 II/III 层神经元中诱导持久的癫痫样活性。

In vivo methylmercury exposure induced long-lasting epileptiform activity in layer II/III neurons in cortical slices from the rat.

机构信息

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.

出版信息

Toxicol Lett. 2010 Mar 15;193(2):138-43. doi: 10.1016/j.toxlet.2009.12.017. Epub 2010 Jan 4.

Abstract

Prenatal and postnatal methylmercury (MeHg) exposure has been shown to increase neuronal excitability and seizure susceptibility. To determine if early postnatal MeHg exposure causes a similar effect, we examined changes in field potentials in layer II/III neurons in cortical slices of rat following in vivo MeHg treatment. Rats received 0 (0.9% NaCl), 0.75 mg/kg/day or 1.5mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which cortical slices were prepared for field potential recordings. In slices from rats treated with vehicle, single pulse stimulation of layer IV of cortical slices induced a typical field excitatory postsynaptic potential (fEPSP) with a single spike. This type of fEPSPs was also seen in slices from rats with 15 day treatment with 0.75 mg/kg/day or 1.5mg/kg/day MeHg. However, 30-day treatment with either MeHg dose resulted in fEPSPs with multiple spikes (epileptiform activity) in 40% of animals examined. This epileptiform activity remained observable in 50-60% animals in which MeHg exposure had been terminated for 30 days. However, slices from control animals still showed fEPSPs with single spike. Thus, these data suggest that postnatal MeHg exposure in vivo altered neuronal excitability and induced a long-lasting hyperexcitability in cortical neurons.

摘要

产前和产后甲基汞(MeHg)暴露已被证明会增加神经元的兴奋性和癫痫易感性。为了确定产后早期 MeHg 暴露是否会产生类似的影响,我们研究了体内 MeHg 处理后大鼠皮质切片中 II/III 层神经元的场电位变化。大鼠在出生后第 5 天开始接受 0(0.9%NaCl)、0.75mg/kg/天或 1.5mg/kg/天的 MeHg 皮下注射,连续 15 或 30 天,然后制备皮质切片进行场电位记录。在接受载体处理的大鼠的切片中,对皮质切片 IV 层的单次脉冲刺激诱导具有单个尖峰的典型场兴奋性突触后电位(fEPSP)。在接受 0.75mg/kg/天或 1.5mg/kg/天 MeHg 治疗 15 天的大鼠的切片中也观察到了这种类型的 fEPSP。然而,用两种 MeHg 剂量处理 30 天导致 40%的动物出现具有多个尖峰的 fEPSP(癫痫样活动)。在 MeHg 暴露已经终止 30 天的 50-60%的动物中,这种癫痫样活动仍然可观察到。然而,对照动物的切片仍显示具有单个尖峰的 fEPSP。因此,这些数据表明,体内产后 MeHg 暴露改变了神经元的兴奋性,并诱导了皮质神经元的长期超兴奋性。

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