Stein Edward J, Filho Nylson G da Silveira, Machado Danilo C, Hipólide Débora C, Barlow Karen, Nobrega José N
Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont., M5T 1R8 Canada; Pharmacology Department, University of Toronto, Toronto, Ont., Canada.
Biopsychology Department, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Psychoneuroendocrinology. 2009 Feb;34(2):281-286. doi: 10.1016/j.psyneuen.2008.09.005. Epub 2008 Oct 17.
While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha1 subtype (TR-alpha1) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha1 mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha1 mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha1 mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha1 mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha1 mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions.
尽管大量临床证据表明甲状腺激素（THs）与抑郁症有关，但这种关联的具体性质仍不清楚。α1亚型（TR-α1）是大脑中最丰富的甲状腺激素受体。在此，我们研究了抑郁症慢性轻度应激（CMS）模型中TR-α1 mRNA的变化。将大鼠暴露于CMS方案3周，这导致蔗糖偏好（快感缺失指标）逐渐降低。然后在处死前2周，每天用丙咪嗪（IMI，10mg/kg）或赋形剂（VEH）处理，之后对全脑进行TR-α1 mRNA的定量原位杂交分析。结果表明，VEH处理的CMS诱导大脑中TR-α1 mRNA广泛降低。相反，在处死前最后2周接受IMI的CMS暴露大鼠显示蔗糖偏好完全恢复。此外，这些动物的脑TR-α1 mRNA水平与接受SAL或IMI的非应激对照相似。这些结果表明，脑TR-α1 mRNA水平对CMS效应非常敏感。IMI逆转CMS的快感缺失和TR-α1效应表明，TR-α1可能在应激诱导的抑郁症状及其通过抗抑郁干预的逆转中均起作用。
