Constantinou Caterina, Bolaris Stamatis, Valcana Theony, Margarity Marigoula
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Patras 265 00, Greece.
Neurosci Res. 2005 Mar;51(3):235-41. doi: 10.1016/j.neures.2004.11.005. Epub 2005 Jan 7.
We have previously reported that short-term LiCl-treatment affects the kinetic characteristics of thyroid hormone binding in adult rat brain (Bolaris, S., Margarity, M., Valcana, T., 1995. Effects of LiCl on triiodothyronine (T3) binding to nuclei from rat cerebral hemispheres. Biol. Psychiatry 37, 106-111); however, the mechanism underlying the above effects of LiCl administration is yet to be determined. In this study, the effects of lithium within one day after its administration (5 mmol/kg BW) on the relative expression of thyroid hormone receptor isoforms and on the cytoplasmic and synaptosomal thyroid hormone availability in adult rat cerebral hemispheres were examined. Although short-term LiCl-treatment did not affect the levels of triiodothyronine either in the synaptosomal or in the cytoplasmic fraction 24 h after LiCl administration, the cytoplasmic availability of thyroxin was lower. In addition, 24 h after the administration of lithium the mRNA levels of the TRalpha1 isoform (T3 binding) increased while the relative expression of the TRalpha2 variant (non-T3 binding) was decreased. Notably, the decrease of the TRalpha2 mRNA levels was also observed 4h after LiCl administration. The expression levels of the TRbeta1 isoform were unaffected in any interval examined. The present study suggests that short-term lithium treatment regulates the relative expression of TRs in an isoform-specific manner and affects the cytoplasmic availability of thyroxin in adult rat brain.
我们之前曾报道,短期给予氯化锂会影响成年大鼠大脑中甲状腺激素结合的动力学特征(博拉里斯,S.,马加里蒂,M.,瓦尔卡纳,T.,1995年。氯化锂对三碘甲状腺原氨酸(T3)与大鼠大脑半球细胞核结合的影响。《生物精神病学》37卷,第106 - 111页);然而,氯化锂给药产生上述影响的潜在机制尚待确定。在本研究中,检测了成年大鼠大脑半球在给予氯化锂(5 mmol/kg体重)一天内,锂对甲状腺激素受体亚型相对表达以及细胞质和突触体中甲状腺激素可用性的影响。尽管短期给予氯化锂在给药后24小时对突触体或细胞质部分中的三碘甲状腺原氨酸水平均无影响,但甲状腺素的细胞质可用性较低。此外,给予锂24小时后,TRα1亚型(T3结合)的mRNA水平升高,而TRα2变体(非T3结合)的相对表达降低。值得注意的是,在给予氯化锂4小时后也观察到TRα2 mRNA水平下降。在任何检测的时间段内,TRβ1亚型的表达水平均未受影响。本研究表明,短期锂治疗以亚型特异性方式调节甲状腺激素受体的相对表达,并影响成年大鼠大脑中甲状腺素的细胞质可用性。