Pre- and postnatal propylthiouracil-induced hypothyroidism impairs synaptic transmission and plasticity in area CA1 of the neonatal rat hippocampus.
Pre- and postnatal propylthiouracil-induced hypothyroidism impairs synaptic transmission and plasticity in area CA1 of the neonatal rat hippocampus.
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DOI：
10.1210/en.2003-0395
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发表时间：
2003-09
期刊：
影响因子：
4.8
通讯作者：
L. Sui;Mary E. Gilbert;Mary E. Gilbert
中科院分区：
文献类型：
--
作者：
L. Sui;Mary E. Gilbert;Mary E. Gilbert
甲状腺激素对新生儿大脑发育至关重要。众所周知，在发育的关键时期，甲状腺激素不足会损害认知功能。然而，甲状腺功能减退动物学习障碍的机制还不清楚。由于突触功能受损可能导致认知缺陷，因此目前的研究测试了发育期间甲状腺激素不足是否会改变海马突触功能的定量特征。发育中的大鼠在子宫内和出生后暴露于0，3，或10 ppm丙基硫氧嘧啶（PTU），甲状腺激素合成抑制剂，从妊娠d 6至出生后第30天（PN）的母鼠饮用水。在PN 21和PN 30之间的后代海马脑片的CA 1区，分别从辐射层和锥体细胞层记录兴奋性突触后电位和群体尖峰。通过比较组间的输入-输出关系来评估基线突触传递。记录成对脉冲易化、成对脉冲抑制、长时程增强和长时程抑制，以检查短时程和长时程突触可塑性。PTU以剂量依赖性方式降低甲状腺激素，减少体重增加，并延迟睁眼。兴奋性突触传递增加发育暴露PTU。甲状腺激素不足也与剂量依赖性减少配对脉冲促进和长时程增强的兴奋性突触后电位和消除配对脉冲抑郁症的人口尖峰。结果表明，甲状腺激素不足损害发育中大鼠海马CA 1区突触通讯的功能完整性，并建议这些变化可能有助于与发育性甲状腺功能减退症相关的学习缺陷。
Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.