Prenatal melamine exposure impairs cognitive flexibility and hippocampal synaptic plasticity in adolescent and adult female rats
Prenatal melamine exposure impairs cognitive flexibility and hippocampal synaptic plasticity in adolescent and adult female rats
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产前三聚氰胺暴露损害青少年和成年雌性大鼠的认知灵活性和海马突触可塑性
DOI：
10.1016/j.pbb.2019.172791
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发表时间：
2019-11-01
影响因子：
3.6
通讯作者：
Sun, Wei
中科院分区：
文献类型：
--
作者：
An, Lei;Li, Jia;Sun, Wei
产前三聚氰胺暴露（PME）会影响青春期雄性大鼠的空间认知并损害突触功能。引人注目的是，这些影响可以持续到成年。目前的实验研究了是否会在雌性后代中观察到 PME 引起的行为缺陷，以及这些影响如何随年龄（青少年和成人）而变化。雌性大鼠在整个妊娠期 (GD) 接触三聚氰胺后，在出生后第 36 天 (PD36) 和 PD90 使用水迷宫任务测试它们的空间认知。从海马 Schaffer 侧枝到 CA1 区域记录长时程增强 (LTP) 和长时程抑制 (LTD)。结果表明，PME 导致严重的逆转学习缺陷，并扰乱 PD36 和 PD90 的 LTD。此外，PME 并不影响 LTP，尽管在青少年 PME 治疗组中观察到的 fEPSP 斜率低于成人 PME 治疗组。此外，PME 不会引起突触修饰阈值的水平移动，但会导致 1.0 Hz 低频刺激 (LFS) 下的频率响应曲线向下移动。然而，配对脉冲促进（PPF）比和输入/输出功能没有受到影响。尽管 NMDA 受体 NR1 和 NR2B 亚基的表达在 PD36 时均减少，但 NR1 水平在 PD90 时并未受到影响。这些发现表明，PME 会损害青少年和成年女性的空间记忆，而通过抑制 NMDAR 表达而导致的海马突触功能损害可能在这些影响中发挥了作用。
Prenatal melamine exposure (PME) affects spatial cognition in adolescent male rats and impairs synaptic functions. Strikingly, these effects can persist into adulthood. The current experiments examined whether PME-induced behavioral defects would be observed in female offspring, and how these effects varied with age (adolescent and adult). After female rats were exposed to melamine through their entire gestational period (GD), their spatial cognition was tested using water maze tasks at postnatal day 36 (PD36) and PD90. Long-term potentiation (LTP) and long-term depression (LTD) were recorded from the hippocampal Schaffer collaterals to the CAl area. Results indicated that PME led to substantial reversal learning deficits and disrupted LTD at both PD36 and PD90. Additionally, PME did not affect LTP, although a lower fEPSP slope was observed in the adolescent PME-treated group than in the adult PME-treated group. Additionally, PME did not induce a horizontal shift in the synaptic modification threshold but caused a downward shift of the frequency-response curve at the low-frequency stimulation (LFS) of 1.0 Hz. However, the paired-pulse facilitation (PPF) ratio and the input/output function were not affected. Although the expression of both NR1 and NR2B subunits of NMDA receptors were diminished at PD36, the NR1 level was not affected at PD90. These findings suggest that PME impairs spatial memory in adolescent and adult females, and the impairments of hippocampal synaptic function via the inhibition of NMDAR expression may play a role in these effects.