Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants.
Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants.
复制标题
应激和抗抑郁药物对弓状核和蓝斑中神经肽 Y mRNA 表达的差异调节。
DOI：
10.1046/j.1365-2826.2000.00451.x
复制
发表时间：
2000
影响因子：
3.2
通讯作者：
Gold,PW
中科院分区：
文献类型：
--
作者：
Makino,S;Baker,RA;Smith,MA;Gold,PW
在大鼠中，循环皮质酮和胰岛素参与下丘脑神经肽 Y (NPY) 系统的调节，而该系统又参与下丘脑-垂体-肾上腺 (HPA) 轴的调节。由于 HPA 轴和应激反应性在抑郁症等疾病中发生改变，我们使用原位杂交组织化学研究了应激和抗抑郁药物治疗对弓状核和蓝斑 NPY mRNA 表达的影响之间的相互作用。急性（2小时）和反复固定（每天2小时，持续14天）后，血浆皮质酮浓度升高，而胰岛素浓度降低。急性和反复固定后，弓状核中 NPY mRNA 的表达显着增加，但蓝斑中的表达没有变化。接受全身皮质酮替代（ADX+CORT）的肾上腺切除大鼠，其皮质酮浓度在重复应激期间维持在约50-100ng/ml，显示血浆胰岛素减少，弓状核NPY mRNA增加，与假手术大鼠中观察到的情况相似，表明NPY mRNA水平的变化与循环胰岛素的关系比与循环皮质酮的关系更密切。相反，重复应激后ADX+CORT大鼠的蓝斑NPY mRNA表达量显着高于假手术大鼠。与盐水治疗的大鼠相比，去甲基丙咪嗪 (DMI) 治疗 24 天不影响皮质酮或胰岛素的基础血浆浓度或弓形核 NPY mRNA 表达，但显着降低蓝斑 NPY mRNA 的基础水平。重复固定（每天 2 小时，持续 4 天）后，DMI 显着降低了应激诱导的蓝斑 NPY mRNA 水平的升高，但增强了应激诱导的弓状核 NPY mRNA 表达的升高。这些结果表明：（1）应激大鼠弓形核NPY mRNA表达的增加密切伴随血浆胰岛素浓度的降低； (2)在血浆皮质酮没有变化的情况下，NPY mRNA表达增加； (3)地昔帕明治疗增强了应激对弓状核NPY mRNA表达的影响，但阻断了应激诱导的蓝斑核NPY mRNA表达的重复增加。因此，弓状核和蓝斑中的 NPY mRNA 表达对应激和抗抑郁药物地昔帕明的影响敏感，但弓状核 NPY 系统的调节机制与蓝斑 NPY 系统不同。该结果进一步证明了循环胰岛素在调节弓状核 NPY 系统中的重要性。
In rats, circulating corticosterone and insulin are involved in regulation of the hypothalamic neuropeptide Y (NPY) system, which in turn, is involved in regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis. Since the HPA axis and stress responsivity is altered in diseases such as depression, we investigated interactions between the effects of stress and antidepressant drug treatment on arcuate nucleus and locus coeruleus NPY mRNA expressions usingin‐situhybridization histochemistry. After acute (2 h) and repeated immobilization (2 h daily, for 14 days), plasma concentrations of corticosterone increased, and those of insulin decreased. The expression of NPY mRNA was significantly increased in the arcuate nucleus, but was unchanged in the locus coeruleus following acute and repeated immobilization. Adrenalectomized rats with systemic corticosterone replacement (ADX+CORT), whose corticosterone concentration was maintained at ≈50–100 ng/ml during repeated stress, showed a decrease in plasma insulin and an increase in arcuate nucleus NPY mRNA similar to that observed in sham rats, suggesting that changes in NPY mRNA levels are more closely tied to circulating insulin than to circulating corticosterone. In contrast, locus coeruleus NPY mRNA expressions in ADX+CORT rats were significantly higher than those in sham rats after repeated stress. Desmethylimipramine (DMI) treatment for 24 days did not affect basal plasma concentrations of corticosterone or insulin, or arcuate nucleus NPY mRNA expressions, but significantly decreased basal levels of locus coeruleus NPY mRNA compared to saline‐treated rats. After repeated immobilization (2 h daily, for 4 days), DMI significantly reduced the stress‐induced rise in locus coeruleus NPY mRNA levels, but potentiated the stress‐induced rise in arcuate nucleus NPY mRNA expression. These results demonstrate that: (1) the increase in arcuate nucleus NPY mRNA expressions in stressed rats closely follows the decrease in plasma concentrations of insulin; (2) increases in NPY mRNA expressions occur in the absence of changes in plasma corticosterone; and (3) desipramine treatment potentiated the effect of stress on arcuate nucleus NPY mRNA expressions, but blocked the repeated stress‐induced increase in locus coeruleus NPY mRNA expressions. Thus, NPY mRNA expression in the arcuate nucleus and the locus coeruleus is sensitive to the effects of stress and to the antidepressant drug desipramine, but the arcuate nucleus NPY system is regulated by different mechanisms than the locus coeruleus NPY system. The results provide further evidence for the importance of circulating insulin in the regulation of the arcuate nucleus NPY system.