Gerges Nashaat Z, Alkadhi Karim A
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77204-5515, USA.
Hippocampus. 2004;14(1):40-5. doi: 10.1002/hipo.10165.
Thyroid hormone activates extracellular signal-regulated kinases (ERK1 and ERK2), which are important in late long-term potentiation (L-LTP). The aim of this study was to determine the possible mechanism underlying the impairment of L-LTP as a result of hypothyroidism. We investigated the effect of hypothyroidism on L-LTP of the two associative pathways in the hippocampus: the Schaffer collateral synapses and the perforant path synapses. We also examined the effect of hypothyroidism on ERK1 and ERK2 levels in both the CA1 and dentate gyrus (DG) regions of the hippocampus. Electrophysiological recordings from hippocampi of anesthetized rats show that hypothyroidism impairs L-LTP in CA1 region, but not in the DG. Western blot analysis of the CA1 region shows that hypothyroidism decreases phosphorylated ERK1 and ERK2 levels without affecting their total levels. In the DG of the hypothyroid rat, however, there was no significant change in the levels of phosphorylated or total ERKs. The correlation between the effect of hypothyroidism on L-LTP and enzyme levels suggests that hypothyroidism-induced impairment of L-LTP in CA1 may be due to decreased levels of phosphorylated ERK1 and ERK2.
甲状腺激素可激活细胞外信号调节激酶（ERK1和ERK2），这在晚期长时程增强（L-LTP）中很重要。本研究的目的是确定甲状腺功能减退导致L-LTP受损的潜在机制。我们研究了甲状腺功能减退对海马体中两条联合通路的L-LTP的影响：谢弗侧支突触和穿通通路突触。我们还检测了甲状腺功能减退对海马体CA1区和齿状回（DG）中ERK1和ERK2水平的影响。对麻醉大鼠海马体的电生理记录显示，甲状腺功能减退会损害CA1区的L-LTP，但不会影响DG区。对CA1区的蛋白质免疫印迹分析表明，甲状腺功能减退会降低磷酸化ERK1和ERK2的水平，但不影响其总水平。然而，在甲状腺功能减退大鼠的DG区，磷酸化或总ERK的水平没有显著变化。甲状腺功能减退对L-LTP的影响与酶水平之间的相关性表明，甲状腺功能减退引起的CA1区L-LTP受损可能是由于磷酸化ERK1和ERK2水平降低所致。
