Villar M J, Meister B, Cortés R, Schalling M, Morris M, Hökfelt T
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1990;36(1):181-99. doi: 10.1016/0306-4522(90)90361-7.
Hypothalamic magnocellular neurons of the paraventricular and supraoptic nuclei contain several peptides and non-peptide putative neurotransmitters co-existing with vasopressin and oxytocin. However, the functional role of these substances is still unknown. In the present paper the temporal course of changes in the expression of vasopressin, oxytocin, galanin, cholecystokinin, dynorphin and tyrosine hydroxylase in magnocellular hypothalamic neurons of rats subjected to hypophysectomy was examined. Following different survival times the animals were processed either for immunohistochemistry with antibodies against the above mentioned peptides or for in situ hybridization with synthetic oligonucleotide probes complementary to the mRNAs encoding for the peptides. The results obtained showed a marked rise in vasopressin mRNA levels at two days followed by a decrease up to 36 days of survival. Oxytocin mRNA responded to the lesion with a transient decrease, with its lowest values between five and seven days. This was followed by a recovery which almost reached normal values at 36 days of survival. The results also showed a marked, transient activation of the synthetic pathway for galanin and cholecystokinin. The numbers of cells expressing these peptides were maximal between five and seven days, and the respective mRNA levels were significantly increased at these survival times. This was followed by a decrease in the amount of galanin- and cholecystokinin-like immunoreactivity as well as in the levels of their respective mRNAs. Dynorphin-like immunoreactivity showed a course similar to that of galanin and cholecystokinin in operated animals. However, the amounts of dynorphin mRNA were significantly increased at two days, but were followed by a reduction at five days and remained low throughout the different survival times tested. The experiments performed with the tyrosine hydroxylase antibodies and probe showed undetectable levels of the enzyme and its mRNA in normal and hypophysectomized animals. These results demonstrate that, in magnocellular hypothalamic neurons, expression of several peptides occur in differential ways after hypophysectomy. The possibility is discussed that these changes represent part of the mechanisms underlying the process of degeneration and regeneration known to occur in magnocellular hypothalamic neurons after hypophysectomy.
室旁核和视上核的下丘脑大细胞神经元含有几种肽类和非肽类假定神经递质，它们与血管加压素和催产素共存。然而，这些物质的功能作用仍然未知。在本文中，研究了垂体切除大鼠下丘脑大细胞神经元中血管加压素、催产素、甘丙肽、胆囊收缩素、强啡肽和酪氨酸羟化酶表达变化的时间进程。在不同的存活时间后，对动物进行处理，要么用针对上述肽的抗体进行免疫组织化学检测，要么用与编码这些肽的mRNA互补的合成寡核苷酸探针进行原位杂交。获得的结果显示，血管加压素mRNA水平在两天时显著升高，随后在存活至36天时下降。催产素mRNA对损伤的反应是短暂下降，在五到七天时达到最低值。随后是恢复，在存活36天时几乎达到正常值。结果还显示，甘丙肽和胆囊收缩素的合成途径有明显的短暂激活。表达这些肽的细胞数量在五到七天时最多，在这些存活时间各自的mRNA水平显著增加。随后，甘丙肽样和胆囊收缩素样免疫反应性的量以及它们各自mRNA的水平下降。在手术动物中，强啡肽样免疫反应性显示出与甘丙肽和胆囊收缩素相似的变化过程。然而，强啡肽mRNA的量在两天时显著增加，但在五天时下降，并且在整个测试的不同存活时间内保持较低水平。用酪氨酸羟化酶抗体和探针进行的实验表明，在正常和垂体切除的动物中均未检测到该酶及其mRNA的水平。这些结果表明，在垂体切除后，下丘脑大细胞神经元中几种肽的表达以不同方式发生。讨论了这些变化可能代表垂体切除后下丘脑大细胞神经元中已知的变性和再生过程潜在机制的一部分。
