Baker R A, Herkenham M
Section of Functional Neuroanatomy, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Comp Neurol. 1995 Aug 7;358(4):518-30. doi: 10.1002/cne.903580405.
The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin-releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series in situ hybridization histochemistry was used to quantify levels of eight accurate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin-releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptide Y mRNA was contained in 18% of the fluorogold-positive neurons in the arcuate, proopiomelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin-releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adrenalectomized rats.
在两个系列的实验中,研究了下丘脑弓状核在介导肾上腺切除术后室旁核促肾上腺皮质激素释放激素mRNA水平升高方面可能发挥的作用。在第一个系列实验中,采用原位杂交组织化学方法,对可能将肾上腺类固醇反馈传递至室旁核的神经元中8种精确核神经肽和神经递质mRNA的水平进行定量分析。在第二个系列实验中,结合逆行追踪和原位杂交组织化学方法,对弓状核向下丘脑室旁核的神经肽能投射进行了特征描述。尽管肾上腺切除术后14天,室旁核促肾上腺皮质激素释放激素(增加60%)和垂体阿黑皮素原mRNA水平(增加6倍)有所升高,但弓状核中阿黑皮素原、神经肽Y、生长抑素、甘丙肽、强啡肽、酪氨酸羟化酶、谷氨酸脱羧酶和糖皮质激素受体的mRNA水平并未改变。通过将逆行示踪剂荧光金注入室旁核,实现了对弓状核-室旁核投射的神经肽能特征描述;利用针对荧光金的多克隆抗血清结合针对神经肽Y、阿黑皮素原或生长抑素的寡核苷酸探针,对逆行标记的神经元进行特征分析。在这些神经元中,三种弓状核神经肽中,神经肽Y mRNA存在于18%的弓状核荧光金阳性神经元中,阿黑皮素原mRNA存在于8%的神经元中,生长抑素mRNA存在于6%的神经元中。总体而言,两个实验的结果均表明,弓状核-室旁核神经肽Y、阿黑皮素原和生长抑素投射对长期(14天)缺乏肾上腺类固醇不敏感。这些投射以及其他弓状核神经递质和神经肽系统似乎并未导致肾上腺切除14天大鼠室旁核促肾上腺皮质激素释放激素mRNA水平或垂体阿黑皮素原mRNA水平持续升高。