宫内铅暴露降低海马NMDAR-2AmRNA表达及影响成年后大鼠海马长时程增强

本研究观察了宫内低水平铅暴露对成年后大鼠海马穿通纤维 -齿状回颗粒细胞层 L TP(长时程增强 )及 2 1日龄大鼠海马 NMDAR- 2 A(N-甲基 - D-天门冬氨酸受体 2 A亚型 ) m RNA表达的影响 ,从分子水平探讨铅神经毒性的远期危害作用。雌性大鼠从交配前 10天开始直到断乳 (产后 2 1天 )饮用含 0 .5g/ L 或 2 g/ L 的醋酸铅水 ,在仔鼠 70～ 90日龄时 ,利用在位电生理技术测定大鼠海马齿状回由强直刺激诱导的群峰电位。结果表明 ,虽然铅暴露大鼠的血铅水平已降至 10 0 μg/ L 以下 ,但海马齿状回 L TP的幅度在6 0 min时低铅组分别为 (139± 41) %和 (136± 31) % ,在高铅组为 (15 1± 32 ) %和 (145± 30 ) %而对照组均显著较高 ,分别为 (311± 112 ) %和 (319± 114) %。提示发育早期铅暴露对学习记忆的损害可能持续到成年期。以原位杂交法检测 2 1日龄仔鼠海马 DG(齿状回 )、CA1及 CA2区 NMDAR- 2 A m RNA表达情况。对 DG区颗粒细胞层 ,CA1及 CA2区锥体细胞层分析表明 ,中毒组动物 NMDAR- 2 A m RNA的表达明显低于对照组 ,下降幅度分别为 34%、37%和 44 %。因为 NMDA受体通道开放是 L TP触发之基础 ,所以宫内低铅暴露对 NMDA受体 m RNA表达的影响很可能是铅对 L TP远期危害的关键分子机制。

Effect of lead exposure during pregnancy on hippocampal long-term potentiation and expression of NMDAR-2A mRNA in the off-spring rats

Chronic lead exposure during brain development is known to affect cognitive and behavioral functions in children and animals. The lead exposure on pregnant rats was used as a model to examine the effects of lead on the long term potentiation(LTP) in hippocampal dentate gyrus(DG) region in vivo and the expression of NMDAR-2A mRNA by in situ hybridization in the off springs. Female rats were exposed to 0 5g/L or 2g/L lead acetate in drinking water since 10 days before mating to weaning. The filial rats of 70—90 days old with blood lead levels below 100μg/L were prepared for recording their DG-evoked population spike(PS) in the hippocampal DG area in vivo. The results showed that the range of LTP were (136±31)% in low lead group,(145±30)% in high lead group, and (319±114)% in control group. The reduction of NMDAR-2A mRNA expression 34%—44% in the granule and pyramidal cell layers caused by lead were seen in 21 days old rats. It indicated that the cognitive deficits induced by low level lead exposure in early stage of life may persist to adulthood, and the modified NMDAR gene expression may play a key role in the cognitive deficits associated with lead exposure during development