Ruiz-Marcos A, Cartagena-Abella P, Martinez-Galan J R, Calvo R, Morreale de Escobar G, Escobar del Rey F
Unidad de Neuroanatomía, Instituto Cajal, Madrid, Spain.
J Neurobiol. 1994 Jul;25(7):808-18. doi: 10.1002/neu.480250706.
In contrast to the permanent alterations resulting from neonatal hypothyroidism, the effects of juvenile-onset hypothyroidism on the number and distribution of spines along the apical shaft of pyramidal neurons of the visual cortex appeared to be potentially reversible with adequate thyroxine (T4) therapy (Ruiz-Marcos et al., 1980, Brain Res. 185:91-102 and 1982, Brain Res. 239:559-574). Treatment with 0.20 or 1.50 micrograms T4/100 g body weight per day had, however, only partially reversed the changes induced by juvenile-onset hypothyroidism. We here study whether or not a higher dose of T4 would totally reverse these effects. A group of rats were thyroid-ectomized at 40 days of age, and injected once daily with placebo or T4 (1.75 micrograms/100 g BW per day) from 70 to 90 days of age, a group on 1.50 micrograms being included to compare with previous results. Spine number and distribution were measured, as well as the concentrations of T4 and triiodothyronine (T3) in plasma, liver and brain. The activities of two hepatic enzymes were measured as thyroid hormone-sensitive biological end points. The 1.75-micrograms dose restored spine number to 88% of normal values and was markedly more effective than the 1.50-micrograms dose, which increased it to 68%. The degree of restoration appeared related to the concentration of T3. It is concluded that the changes caused by juvenile-onset hypothyroidism in the number and distribution of dendritic spines along the apical shafts of pyramidal neurons are reversible, although complete restoration might require a higher dose of T4, a continuous mode of administration, or longer period of treatment.
与新生儿甲状腺功能减退所导致的永久性改变不同，幼年型甲状腺功能减退对视皮层锥体细胞顶树突棘数量及分布的影响，在给予足够的甲状腺素（T4）治疗后似乎有可能逆转（Ruiz-Marcos等人，1980年，《脑研究》185:91 - 102；1982年，《脑研究》239:559 - 574）。然而，每天给予0.20或1.50微克T4/100克体重的治疗，仅部分逆转了幼年型甲状腺功能减退所引起的变化。我们在此研究更高剂量的T4是否能完全逆转这些影响。一组大鼠在40日龄时进行甲状腺切除，并在70至90日龄期间每天注射一次安慰剂或T4（1.75微克/100克体重/天），还纳入了一组给予1.50微克T4的大鼠以与先前结果进行比较。测量了树突棘数量和分布，以及血浆、肝脏和大脑中T4和三碘甲状腺原氨酸（T3）的浓度。测量了两种肝脏酶的活性作为甲状腺激素敏感的生物学终点。1.75微克剂量将树突棘数量恢复到正常值的88%，明显比1.50微克剂量更有效，后者将其增加到68%。恢复程度似乎与T3浓度有关。结论是，幼年型甲状腺功能减退引起的锥体细胞顶树突棘数量和分布的变化是可逆的，尽管完全恢复可能需要更高剂量的T4、持续给药方式或更长的治疗时间。
