Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Universidad de Atacama, Facultad de Ciencias Naturales, Departamento de Química y Biología, Copayapu 485, Copiapó, Chile.
Biochim Biophys Acta Mol Basis Dis. 2017 Apr;1863(4):870-883. doi: 10.1016/j.bbadis.2017.01.002. Epub 2017 Jan 11.
Thyroid hormones are vital in the control of multiple body functions, including the correct performance of the brain. Multiple diseases are associated with thyroid gland functioning, including hypothyroidism. To date, little is known regarding the effects of the establishment of this condition at a young age on brain function. Here, we evaluated the effect of hypothyroidism in an early postnatal stage in cognitive abilities with focus on the hippocampus. In our model, hypothyroidism was induced in young rats at 21days of age using 0.05% 6-propyl-2-thiouracil (PTU) for 4weeks reaching significantly lower levels of fT (control: 1.337ng/dL±0.115, PTU: 0.050ng/dL±0.001). Following the induction of hypothyroidism, several cognitive tasks were assessed to investigate the effects of hypothyroidism on cognition performance. We determined that hypothyroidism triggers a significant dysfunction in learning and memory processes observed in the Morris Water Maze were the latency times were higher in PTU rats (controls: 37s; PTU: 57s). The cognitive impairment was correlated with a reduction in hippocampal plasticity with respect to both long-term potentiation (LTP) (control: 1.45, PTU: 1.00) and depression (LTD) (control: 0.71, PTU: 1.01). Furthermore, a decrease in the rate of glucose utilization (control: 223nmol∗mg of protein, PTU:148nmol∗mg of protein) was observed, along with an increase in oxidative stress and a decrease in MAP2 marker in the hippocampus. Our findings suggest that the induction of hypothyroidism in a young rat model alters numerous functions at the level of the hippocampus.
甲状腺激素对控制多种身体功能至关重要，包括大脑的正常运作。多种疾病与甲状腺功能有关，包括甲状腺功能减退症。迄今为止，对于在幼年时期就出现这种情况对大脑功能的影响知之甚少。在这里，我们评估了在早期产后阶段甲状腺功能减退症对认知能力的影响，重点是海马体。在我们的模型中，在 21 天大的幼鼠中使用 0.05% 6-丙基-2-硫尿嘧啶（PTU）诱导甲状腺功能减退症 4 周，导致 fT 水平显著降低（对照组：1.337ng/dL±0.115，PTU：0.050ng/dL±0.001）。在诱导甲状腺功能减退症后，评估了多项认知任务，以研究甲状腺功能减退症对认知表现的影响。我们发现，甲状腺功能减退症会引发莫里斯水迷宫中学习和记忆过程的明显功能障碍，PTU 大鼠的潜伏期时间更长（对照组：37s；PTU：57s）。认知障碍与海马体可塑性的降低有关，包括长时程增强（LTP）（对照组：1.45，PTU：1.00）和抑郁（LTD）（对照组：0.71，PTU：1.01）。此外，还观察到葡萄糖利用率降低（对照组：223nmol∗mg 的蛋白质，PTU：148nmol∗mg 的蛋白质），氧化应激增加，海马体中 MAP2 标志物减少。我们的研究结果表明，在幼鼠模型中诱导甲状腺功能减退症会改变海马体水平的多种功能。
