Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 N, 5th Street, Phoenix, AZ 85004, USA.
Brain Res. 2012 Oct 5;1477:19-26. doi: 10.1016/j.brainres.2012.08.020. Epub 2012 Aug 17.
The neuropeptide thyrotropin-releasing hormone (TRH) is recognized to play an important role in controlling energy balance through direct effects on the CNS, although mechanisms explaining the phenomenon are poorly understood. To begin to understand the effects of TRH on CNS control of energy balance, we first mapped neurons expressing the TRH precursor peptide, prepro-TRH (ppTRH) in the paraventricular nucleus of the rat hypothalamus and the surrounding regions. We identified a population of ppTRH-expressing neurons in the juxtaparaventricular region of the lateral hypothalamus (LHAjp) which were stimulated by the satiety signal leptin (2.5μg/kg, IP). Using a model of fetal glucocorticoid (GC) exposure in which pregnant rats were treated with the synthetic GC dexamethasone (DEX) during gestational days 18-21, it was observed that such exposure resulted in reduced numbers of ppTRH-ir neurons in the LHAjp in adult male and female rats, and was accompanied by increased food intake. Our data provide further insight into the biological role of the LHAjp, as well as the potential involvement of TRH neurons within this region in metabolic disease associated with fetal glucocorticoid exposure.
神经肽促甲状腺素释放激素(TRH)被认为通过对中枢神经系统的直接作用在控制能量平衡中发挥重要作用,尽管解释这一现象的机制还知之甚少。为了开始了解 TRH 对中枢神经系统控制能量平衡的影响,我们首先绘制了在大鼠下丘脑室旁核及其周围区域表达 TRH 前体肽 prepro-TRH(ppTRH)的神经元图谱。我们在外侧下丘脑的室旁旁区域(LHAjp)中鉴定出一群表达 ppTRH 的神经元,它们受到饱腹感信号瘦素(2.5μg/kg,IP)的刺激。使用胎儿糖皮质激素(GC)暴露的模型,在妊娠第 18-21 天期间用合成 GC 地塞米松(DEX)处理怀孕的大鼠,观察到这种暴露导致成年雄性和雌性大鼠 LHAjp 中的 ppTRH-ir 神经元数量减少,并伴有食物摄入量增加。我们的数据进一步深入了解了 LHAjp 的生物学作用,以及与胎儿 GC 暴露相关的代谢疾病中该区域内 TRH 神经元的潜在参与。