Department of Physiology, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
PLoS One. 2013 Apr 23;8(4):e61616. doi: 10.1371/journal.pone.0061616. Print 2013.
Ciliary neurotrophic factor (CNTF) induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.
睫状神经营养因子（CNTF）可诱导神经发生，减少摄食，并导致体重减轻。然而，CNTF 发挥作用的中枢机制尚不清楚。我们使用内源性表达 CNTF 受体的 mHypoE-20/2 系来研究 CNTF 对 Ucn-1、Ucn-2、阿黑皮素原、脑源性神经营养因子和神经降压素 mRNA 水平的直接影响。我们发现，10ng/ml CNTF 处理在 48 小时内仅使 Ucn-1 mRNA 显著增加 1.84 倍。然后，我们将 0.5mg/ml CNTF 经侧脑室注射入小鼠，并在暴露后检测其对 Ucn-1 神经元的影响。通过使用针对 c-Fos 和 Ucn-1 的特异性抗体进行双标免疫组织化学染色，我们表明中枢 CNTF 给药可显著激活下丘脑特定区域的 Ucn-1 神经元。总之，我们的研究表明 CNTF 在调节下丘脑 Ucn-1 表达神经元以介导其对能量平衡、神经元增殖/存活和/或神经发生的已知作用方面具有潜在作用。
