Department of Pharmacology, University of Florence, Florence, Italy.
Br J Pharmacol. 2013 Jan;168(2):354-62. doi: 10.1111/j.1476-5381.2012.02137.x.
3-Iodothyronamine (T1AM), an endogenous derivative of thyroid hormones, is regarded as a rapid modulator of behaviour and metabolism. To determine whether brain thyroid hormone levels contribute to these effects, we investigated the effect of central administration of T1AM on learning and pain threshold of mice either untreated or pretreated with clorgyline (2.5 mg·kg(-1) , i.p.), an inhibitor of amine oxidative metabolism.
T1AM (0.13, 0.4, 1.32 and 4 μg·kg(-1) ) or vehicle was injected i.c.v. into male mice, and after 30 min their effects on memory acquisition capacity, pain threshold and curiosity were evaluated by the following tests: passive avoidance, licking latency on the hot plate and movements on the hole-board platform. Plasma glycaemia was measured using a glucorefractometer. Brain levels of triiodothyroxine (T3), thyroxine (T4) and T1AM were measured by HPLC coupled to tandem MS. ERK1/2 activation and c-fos expression in different brain regions were evaluated by Western blot analysis.
T1AM improved learning capacity, decreased pain threshold to hot stimuli, enhanced curiosity and raised plasma glycaemia in a dose-dependent way, without modifying T3 and T4 brain concentrations. T1AM effects on learning and pain were abolished or significantly affected by clorgyline, suggesting a role for some metabolite(s), or that T1AM interacts at the rapid desensitizing target(s). T1AM activated ERK in different brain areas at lower doses than those effective on behaviour.
T1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative-induced memory disorders.
3-碘甲状腺原氨酸（T1AM）是甲状腺激素的一种内源性衍生物，被认为是行为和代谢的快速调节剂。为了确定脑甲状腺激素水平是否有助于这些效应，我们研究了 T1AM 对未经处理或用氯丙嗪（2.5mg·kg(-1)，腹腔注射）预处理的小鼠学习和痛阈的影响，氯丙嗪是一种胺氧化代谢抑制剂。
T1AM（0.13、0.4、1.32 和 4μg·kg(-1)）或载体被脑室注射到雄性小鼠中，30 分钟后，通过以下测试评估其对记忆获得能力、痛阈和好奇心的影响：被动回避、热板舔舐潜伏期和洞板平台上的运动。使用葡萄糖折射计测量血浆血糖水平。通过 HPLC 与串联 MS 测量脑内三碘甲状腺原氨酸（T3）、甲状腺素（T4）和 T1AM 的水平。通过 Western blot 分析评估不同脑区中 ERK1/2 的激活和 c-fos 的表达。
T1AM 以剂量依赖的方式改善学习能力，降低对热刺激的痛阈，增强好奇心并提高血浆血糖水平，而不改变 T3 和 T4 的脑浓度。T1AM 对学习和疼痛的影响被氯丙嗪阻断或显著影响，表明存在某种代谢物（或 T1AM 与快速脱敏的靶标相互作用）。T1AM 在较低剂量下激活不同脑区的 ERK，低于对行为有效的剂量。
T1AM 是一种新型记忆增强剂。这一特征可能对治疗内分泌和神经退行性疾病引起的记忆障碍具有重要意义。
