Sánchez-Huerta K, Pacheco-Rosado J, Gilbert M E
Departamento de Fisiología 'Mauricio Russek', Escuela Nacional de Ciencias Biológicas, IPN, México City, México; Laboratory of Neurochemistry, National Institute of Pediatrics, Mexico City, Mexico.
J Neuroendocrinol. 2015 Jan;27(1):8-19. doi: 10.1111/jne.12229.
Thyroid hormone (TH) is essential for a number of physiological processes and is particularly critical during nervous system development. The hippocampus is strongly implicated in cognition and is sensitive to developmental hypothyroidism. The impact of TH insufficiency in the foetus and neonate on hippocampal synaptic function has been fairly well characterised. Although adult onset hypothyroidism has also been associated with impairments in cognitive function, studies of hippocampal synaptic function with late onset hypothyroidism have yielded inconsistent results. In the present study, we report hypothyroidism induced by the synthesis inhibitor propylthiouracil (10 p.p.m., 0.001%, minimum of 4 weeks), resulted in marginal alterations in excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude in the dentate gyrus measured in vivo. No effects were seen in tests of short-term plasticity, and a minor enhancement of long-term potentiation of the EPSP slope was observed. The most robust synaptic alteration evident in hypothyroid animals was an increase in synaptic response latency, which was paralleled by a failure to maintain normal body temperature under anaesthesia, despite warming on a heating pad. Latency shifts could be reversed in hypothyroid animals by increasing the external heat source and, conversely, synaptic delays could be induced in control animals by removing the heat source, with a consequent drop in body and brain temperature. Thermoregulation is TH- dependent, and anaesthesia necessary for surgical procedures posed a thermoregulatory challenge that was differentially met in control and hypothyroid animals. Minor increases in field potential EPSP slope, decreases in PS amplitudes and increased latencies are consistent with previous reports of hypothermia in naive control rats. We conclude that failures in thyroid-dependent temperature regulation rather than direct action of TH in synaptic physiology are responsible for the observed effects. These findings stand in contrast to the synaptic impairments observed in adult offspring following developmental TH insufficiency, and emphasise the need to control for the potential unintended consequences of hypothermia in the interpretation of hypothyroid-induced changes in physiological systems, most notably synaptic transmission.
甲状腺激素（TH）对许多生理过程至关重要，在神经系统发育过程中尤为关键。海马体与认知密切相关，且对发育性甲状腺功能减退敏感。胎儿和新生儿期TH不足对海马体突触功能的影响已得到相当充分的研究。尽管成人期甲状腺功能减退也与认知功能受损有关，但关于迟发性甲状腺功能减退对海马体突触功能影响的研究结果并不一致。在本研究中，我们报告了用合成抑制剂丙硫氧嘧啶（10 ppm，0.001%，至少4周）诱导的甲状腺功能减退，导致在体测量的齿状回兴奋性突触后电位（EPSP）和群体峰电位（PS）幅度出现轻微改变。在短期可塑性测试中未观察到影响，且观察到EPSP斜率的长时程增强有轻微增加。甲状腺功能减退动物中最明显的突触改变是突触反应潜伏期延长，这与在麻醉状态下尽管使用加热垫保暖但仍无法维持正常体温相伴。通过增加外部热源可使甲状腺功能减退动物的潜伏期变化逆转，相反，通过移除热源可在对照动物中诱导突触延迟，随之身体和脑温下降。体温调节依赖于TH，手术所需的麻醉对体温调节构成了挑战，对照动物和甲状腺功能减退动物对此的应对方式有所不同。场电位EPSP斜率轻微增加、PS幅度降低和潜伏期延长与先前关于未处理的对照大鼠体温过低的报道一致。我们得出结论，甲状腺依赖的体温调节失败而非TH在突触生理学中的直接作用是导致观察到的效应的原因。这些发现与发育性TH不足后成年子代中观察到的突触损伤形成对比，并强调在解释甲状腺功能减退引起的生理系统变化（最显著的是突触传递）时需要控制体温过低可能产生的意外后果。
