Gilbert M E
Neurotoxicology Division (MD-B105-05), National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Brain Res Dev Brain Res. 2004 Jan 31;148(1):11-8. doi: 10.1016/j.devbrainres.2003.09.018.
Transient reductions in thyroid hormone during critical periods of brain development can have devastating and irreversible effects on neurological function. The hippocampus is a brain region sensitive to thyroid hormones and is a necessary substrate for some forms of learning and memory. Subregions within the hippocampus display distinct ontogenetic profiles and have shown differential vulnerability to some indices of thyrotoxic insult. Synaptic function can be readily assessed in the hippocampus, yet little information exists on the consequences of early thyroid hormone insufficiency on the neurophysiological integrity of this structure. Previous work has examined the long-term consequences of perinatal hypothyroidism on neurophysiology of the dentate gyrus of the hippocampal formation. The current study reveals that alterations in synaptic function also exist in area CA1, and some differences in the pattern of effects are evident between the two hippocampal subfields. Developing rats were transiently exposed to the thyrotoxicant, propylthiouracil (PTU; 0 or 15 ppm), through the drinking water of pregnant dams beginning on gestational day 18. This regimen markedly reduced circulating levels of thyroid hormones and stunted pup growth. PTU exposure was terminated on postnatal day (PN) 21 and electrophysiological assessments were conducted by recording field potentials in area CA1 of hippocampal slices derived from adult male offspring. Synaptic transmission, short-term, and long-term synaptic plasticity were assessed. Consistent with observations in the dentate gyrus, somatic population spike amplitudes were reduced in assessments of baseline synaptic transmission of slices from PTU-exposed animals. No differences were identified in excitatory postsynaptic potentials (EPSP). Short-term plasticity of the EPSP as indexed by paired pulse facilitation was markedly impaired by PTU exposure. Long-term potentiation (LTP) of the population spike was enhanced, consistent with findings in dentate gyrus, but no change in EPSP LTP was detected. Perturbations in synaptic function in the hippocampus of adult rats transiently exposed to a period of hormone insufficiency during the perinatal period are likely to contribute to cognitive deficits associated with developmental hypothyroidism.
在大脑发育的关键时期,甲状腺激素的短暂减少会对神经功能产生毁灭性且不可逆转的影响。海马体是对甲状腺激素敏感的脑区,是某些形式学习和记忆的必要基础。海马体内的亚区域呈现出不同的个体发育特征,并且对甲状腺毒症损伤的某些指标表现出不同的易损性。海马体中的突触功能易于评估,但关于早期甲状腺激素不足对该结构神经生理完整性的影响,目前所知甚少。先前的研究探讨了围产期甲状腺功能减退对海马结构齿状回神经生理学的长期影响。当前研究表明,CA1区也存在突触功能改变,并且两个海马亚区之间在效应模式上存在一些差异。从妊娠第18天开始,通过给怀孕母鼠饮用的水使其短暂接触甲状腺毒剂丙硫氧嘧啶(PTU;0或15 ppm),以此处理发育中的大鼠。这种处理方式显著降低了甲状腺激素的循环水平,并阻碍了幼崽的生长。PTU暴露在出生后第21天终止,通过记录成年雄性后代海马切片CA1区的场电位进行电生理评估,评估了突触传递、短期和长期突触可塑性。与在齿状回中的观察结果一致,在对PTU暴露动物的切片进行基线突触传递评估时,体细胞群体峰电位幅度降低。在兴奋性突触后电位(EPSP)方面未发现差异。PTU暴露显著损害了以双脉冲易化指数衡量的EPSP短期可塑性。群体峰电位的长期增强(LTP)增强,这与在齿状回中的发现一致,但未检测到EPSP的LTP变化。成年大鼠在围产期短暂暴露于激素不足时期,其海马体中的突触功能紊乱可能导致与发育性甲状腺功能减退相关的认知缺陷。