Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure
Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure
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DOI：
10.1016/s0006-8993(98)00054-7
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发表时间：
1998-04-20
期刊：
影响因子：
2.9
通讯作者：
McGlothan, JL
中科院分区：
文献类型：
--
作者：
Guilarte, TR;McGlothan, JL
N-甲基-D-天冬氨酸 (NMDA) 受体已被证明在与发育性铅 (Pb) 暴露相关的认知缺陷中发挥着重要作用。在这项研究中，我们研究了低水平 Ph 暴露对发育中的大鼠大脑中 NMDA 受体亚基基因表达的影响。 NR1、NR2A、NR2B和NR2C亚基mRNA原位杂交结果与之前的研究结果一致。出生后不久，大脑中 NR1 和 NR2A mRNA 的水平最低，在 14 或 21 天时达到峰值，随后在 28 天时下降。 NR2B mRNA 水平在早期发育期间最高，并随着动物年龄的增长而下降。 NR2C 亚基 mRNA 仅限于小脑，直到出生第二周才检测到信号。铅暴露对 NR1 和 NR2A 亚基 mRNA 表达产生显着且相反的影响，而 NR2B 或 NR2C 亚基表达没有变化。 Pb诱导的NR1和NR2A亚基mRNA变化主要存在于海马区。 14 日龄铅暴露大鼠的 CA1 (15.3%) 和 CA4 (26.8%) 锥体细胞中海马 NR1 mRNA 水平显着增加。 21 日龄时，仅 CA4 亚区的 NR1 mRNA 仍显着升高（10.3%）。铅暴露导致 14 日龄和 21 日龄海马锥体细胞层和颗粒细胞层 NR2A mRNA 水平降低 (11.9-19.3%)。 28 日龄大鼠小脑中 NR1 mRNA 水平也显着增加 (14.0%)，而 NR2A mRNA 在任何年龄都没有变化。在任何年龄，皮质或皮质下区域的亚基 mRNA 水平均未出现显着变化。本研究中测量的铅诱导的海马 NMDA 受体亚基 mRNA 表达的变化可能会导致受体水平或亚型的改变，并改变需要 NMDA 受体激活的特定神经元连接的发育。 (C) 1998 Elsevier Science B.V.
The N-methyl-D-aspartate (NMDA) receptor has shown to play an important role in the cognitive deficits associated with developmental lead (Pb) exposure. In this study, we examined the effects of low-level Ph exposure on NMDA receptor subunit gene expression in the developing rat brain. The pattern of NR1, NR2A, NR2B, and NR2C subunit mRNA in situ hybridization was consistent with previous studies. Brain levels of NR1 and NR2A mRNAs were lowest shortly after birth, increasing to reach peak levels by 14 or 21 days of age and subsequently decreasing at 28 days of age. NR2B mRNA levels were highest during early development and decreased as the animals aged. NR2C subunit mRNA was restricted to the cerebellum and a signal was not detectable until the second week of life. Lead exposure resulted in significant and opposite effects in NR1 and NR2A subunit mRNA expression with no changes in NR2B or NR2C subunit expression. The Pb-induced changes in NR1 and NR2A subunit mRNA were mainly present in the hippocampus. Hippocampal NR1 mRNA levels were significantly increased in the CA1 (15.3%) and CA4 (26.8%) pyramidal cells from 14-day-old Pb-exposed rats. At 21 days of age, only the NR1 mRNA at the CA4 subfield remained significantly elevated (10.3%). Lead exposure caused reductions of NR2A mRNA levels (11.9-19.3%) in the pyramidal and granule cell layers of the hippocampus at 14 and 21 days of age. NR1 mRNA levels were also significantly increased (14.0%) in the cerebellum of 28-day-old rats with no change in NR2A mRNA at any age. No significant changes in subunit mRNA levels were present in cortical or subcortical regions at any age. The Pb-induced changes in hippocampal NMDA receptor subunit mRNA expression measured in the present study may lead to modifications in receptor levels or subtypes and alter the development of defined neuronal connections which require NMDA receptor activation. (C) 1998 Elsevier Science B.V.