DAMGO和Galantamine对铅暴露大鼠海马DG区突触可塑性的影响和修复作用

发布时间：2018-12-30 15:37

【摘要】：慢性铅暴露引发多重学习记忆和认知能力的损害。海马的突触可塑性是学习记忆的重要细胞模型，得到了广泛的重视和研究，包括长时程增强(long-termpotentiation, LTP)和长时程压抑(long-term depression, LTD)两种重要形式。去增强(Depotentiation, DP)是突触可塑性的另外一种形式。以往的研究结果表明，慢性铅暴露可以损伤海马CA1区和齿状回(dentate gyrus, DG)的LTP/LTD诱导。本文用场电位记录方法研究了μ型阿片受体激动剂DAMGO对慢性铅暴露大鼠突触可塑性损伤的影响和Galantamine对慢性铅暴露大鼠突触可塑性损伤的修复和保护作用。研究方法和结果如下：新生的Wistar大鼠从出生起到断乳通过饮用0.2%醋酸铅溶液染铅。在27-30日龄大鼠海马离体脑片齿状回记录兴奋性突触后电位。结果表明：DAMGO在铅暴露组和control组都诱导得到LTP幅度增加，并且铅暴露组比control组升高更明显。NMDA受体阻断剂AP5不能完全阻断DAMGO诱导的LTP。铅暴露损伤了高频刺激诱导的LTP，DAMGO对这种损伤没有明显的修复，对control组的HFS-LTP也没有明显的影响。结果说明，DAMGO可以在慢性铅暴露组诱导比control组更高的LTP，其机制部分来源于NMDA受体途径的参与；DAMGO对HFS-LTP组别没有明显作用，可能与铅神经毒理作用在两种LTP诱导过程中位点差异有关。新生的Wistar大鼠自出生到成年通过饮用0.2%醋酸铅溶液染铅。在成年大鼠(60-90日龄)的海马齿状回记录兴奋性突触后电位和群峰电位。进行实验前两周起通过腹腔注射为Galantamine组别动物给药(1 mg/100 g体重每天)。结果显示，慢性铅暴露损伤了大鼠海马DG区LTP/DP的诱导，而Galantamine可以显著的升高铅暴露大鼠LTP/DP的幅度，但是在非铅暴露组只有不明显的升高。这个结果提示Galantamine可以逆转铅导致的大鼠突触可塑性损伤，，并且可能是有效的铅所致认知障碍治疗药物。通过以上的实验，我们研究了DAMGO和Galantamine对慢性铅暴露造成的突触可塑性损伤的影响，了解了可能的作用机制。为进一步了解了铅的神经毒理机制，寻求新的治疗途径提供理论支持。
[Abstract]:Chronic lead exposure leads to multiple learning, memory and cognitive impairment. Synaptic plasticity in hippocampus is an important cellular model of learning and memory, which has been widely studied, including long-term potentiation (long-termpotentiation, LTP) and long-term depression (long-term depression, LTD). Deactivation of (Depotentiation, DP) is another form of synaptic plasticity. Previous studies have shown that chronic lead exposure can damage the LTP/LTD induction of CA1 area and (dentate gyrus, DG) in dentate gyrus. The effects of 渭 opioid receptor agonist DAMGO on synaptic plasticity in rats exposed to chronic lead and the repair and protection of Galantamine on synaptic plasticity in rats exposed to chronic lead were studied by field potential recording. The methods and results were as follows: newborn Wistar rats were exposed to lead from birth to weaning by drinking 0.2% lead acetate solution. Excitatory postsynaptic potentials were recorded in the dentate gyrus of 27-30 day old rats. The results showed that the amplitude of LTP induced by DAMGO was increased in both lead exposure group and control group, and that in lead exposure group was significantly higher than that in control group. AP5, a NMDA receptor blocker, could not completely block DAMGO induced LTP.. LTP,DAMGO induced by high frequency stimuli was not significantly repaired by lead exposure, nor did it affect HFS-LTP in control group. The results showed that DAMGO could induce a higher level of LTP, in chronic lead exposure group than that in control group. The mechanism was partly due to the involvement of NMDA receptor pathway. DAMGO had no obvious effect on HFS-LTP group, which might be related to the difference of site in the induction of lead neurotoxicology between the two types of LTP. Newborn Wistar rats were exposed to lead by drinking 0.2% lead acetate solution from birth to adulthood. Excitatory postsynaptic potentials and group peak potentials were recorded in the dentate gyrus of adult rats (60-90 days old). Two weeks before the experiment, animals in the Galantamine group were injected intraperitoneally (1 mg/100 g BW per day). The results showed that chronic lead exposure induced LTP/DP in the DG area of hippocampus of rats, while Galantamine could significantly increase the amplitude of LTP/DP in lead exposed rats, but it was not significantly increased in non-lead exposed group. These results suggest that Galantamine can reverse the synaptic plasticity injury induced by lead in rats and may be an effective therapy for cognitive impairment induced by lead. The effects of DAMGO and Galantamine on synaptic plasticity induced by chronic lead exposure were studied and the possible mechanism was investigated. In order to further understand the neurotoxicological mechanism of lead and seek a new therapeutic approach to provide theoretical support.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R114

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