Department of Cell Biology, University of Linköping Faculty of Health Sciences, Linköping (Sweden).
Restor Neurol Neurosci. 1990 Jan 1;1(5):331-8. doi: 10.3233/RNN-1990-1504.
The effects of thyroid hormone deficiency on the noradrenergic innervation of hippocampus from locus coeruleus (LC) were examined using intraocular double transplants in albino rats. Fetal brainstem pieces containing the nucleus LC were transplanted to the anterior chamber of the eye of thyroidectomized and normal recipients and the brain grafts were allowed to mature for 8 weeks. Pieces of fetal hippocampal formation were introduced into the anterior eye chamber and placed in contact with the LC grafts or placed in previously operated eyes. As evidenced by high performance liquid chromatography, hippocampal transplants in contact with a brainstem graft gradually became hyperinnervated by noradrenergic fibers from these grafts. The levels of norepinephrine were lower in single control grafts and in double grafts in thyroidectomized animals than in control double grafts. Extracellular recordings of single neuronal activity were performed in hippocampal transplants in all 3 groups after 10-14 months in oculo. Superfusion with the α2- adrenergic agonist clonidine and the α-adrenergic antagonist phentolamine elicited significant increases in discharge rate of hippocampal neurons in control double transplants, but not in single hippocampal grafts or in double grafts in thyroidectomized hosts. The β-adrenergic antagonist timolol did not change the neuronal firing rate in any of the 3 groups. Superfusion with penicillin over single hippocampal transplants caused long-lasting increases in slow-wave activity. This increased bioelectric activity remained after the cessation of drug application. A similar increase in slow-wave activity was found in hyperinnervated control double transplants only when penicillin was combined with clonidine or phentolamine. However, the hippocampal portion of double grafts in thyroidectomized recipients readily responded to penicillin with seizures and/or interictal spiking. The data presented here suggest that chronic lack of thyroid hormones leads to significant disturbances of the central noradrenergic transmission in isolated LC-hippocampal circuits.
甲状腺激素缺乏对来自蓝斑核（LC）的去甲肾上腺素能神经支配对海马的影响，使用白化大鼠眼内双移植进行了检查。含有 LC 核的胎脑干片段被移植到甲状腺切除和正常接受者的眼前房，并允许脑移植物成熟 8 周。胎儿海马形成片段被引入眼前房，并与 LC 移植物接触或放置在先前手术的眼中。正如高效液相色谱法所证明的那样，与脑移植接触的海马移植逐渐被来自这些移植的去甲肾上腺素能纤维过度支配。在甲状腺切除动物的单个对照移植物和双移植物中，去甲肾上腺素的水平低于对照双移植物。在眼内 10-14 个月后，在所有 3 组的海马移植中进行了单神经元活动的细胞外记录。用 α2-肾上腺素能激动剂可乐定和 α-肾上腺素能拮抗剂酚妥拉明灌流，可显著增加对照双移植中海马神经元的放电率，但不能增加单个海马移植或甲状腺切除宿主的双移植。β-肾上腺素能拮抗剂噻吗洛尔未改变任何 3 组中的神经元放电率。用青霉素单次灌注单个海马移植会导致慢波活动的持久增加。在药物应用停止后，这种增加的生物电活动仍然存在。在青霉素与可乐定或酚妥拉明联合使用时，仅在高神经支配的对照双移植中发现了类似的慢波活动增加。然而，甲状腺切除受体的双移植物的海马部分容易对青霉素产生癫痫发作和/或发作间尖峰。本文提供的资料表明，慢性缺乏甲状腺激素会导致孤立的 LC-海马回路中的中枢去甲肾上腺素能传递发生重大干扰。
