Lucassen P J, Van Heerikhuize J J, Guldenaar S E, Pool C W, Hofman M A, Swaab D F
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, The Netherlands.
J Neuroendocrinol. 1997 Apr;9(4):297-305. doi: 10.1046/j.1365-2826.1997.t01-1-00583.x.
The paraventricular (PVN) and supraoptic nucleus (SON) demonstrate a striking stability with respect to cell numbers during aging and Alzheimer's disease (AD). Vasopressin (AVP) neurons even become activated during aging as judged from several parameters for neuronal activity, such as increased AVP plasma levels, enlarged nucleolar as well as cell size and an increased size of the Golgi apparatus in AVP-neurons. The activation possibly occurs as compensation for an age-related loss of AVP-receptors in the kidney. As a specific marker for AVP synthesis, we used quantitative in situ hybridization and estimated total amounts of AVP-mRNA in the entire SON and PVN of 14 control subjects and 14 AD patients that were matched for age, fixation time, postmortem delay and storage time of the tissue in paraffin. Following quantification, no differences were observed in total amounts of AVP-mRNA in the SON or PVN between young and old controls or between young and old AD patients, nor between the entire group of controls and AD patients. A significant negative correlation was found between the volume of the AVP-mRNA signal in the AD SON and age while the total amount of mRNA remained the same. This suggests a redistribution of cells or cell compartments in aging. A significant positive relation in both SON and PVN of AD patients was found between storage time of the paraffin-embedded tissue and the total amount of AVP-mRNA. A significant positive relation was present in the PVN, but not SON between pH of the cerebrospinal fluid, which is a marker for agonal state and the total amount of AVP mRNA. The present unchanged AVP-mRNA levels in SON and PVN confirm earlier observations on the stability of cell numbers in these nuclei in aging and AD. Although on the basis of other parameters, AVP-mRNA upregulation was expected, gradual, chronic stimulation over prolonged periods of time may, possibly, induce alternative mechanisms of regulation such as changes in translatability or in mRNA stability.
室旁核（PVN）和视上核（SON）在衰老和阿尔茨海默病（AD）过程中，细胞数量表现出显著的稳定性。从神经元活动的几个参数判断，如抗利尿激素（AVP）血浆水平升高、核仁以及细胞大小增大，以及AVP神经元中高尔基体大小增加，抗利尿激素（AVP）神经元在衰老过程中甚至会被激活。这种激活可能是作为对肾脏中与年龄相关的AVP受体丢失的一种补偿。作为AVP合成的特异性标志物，我们使用定量原位杂交技术，估计了14名对照受试者和14名AD患者的整个SON和PVN中AVP - mRNA的总量，这些受试者在年龄、固定时间、死后延迟时间以及组织在石蜡中的储存时间方面相互匹配。定量后发现，年轻和老年对照之间或年轻和老年AD患者之间，SON或PVN中AVP - mRNA的总量没有差异，整个对照组和AD患者组之间也没有差异。在AD的SON中，AVP - mRNA信号的体积与年龄之间存在显著的负相关，而mRNA的总量保持不变。这表明在衰老过程中细胞或细胞区室发生了重新分布。在AD患者的SON和PVN中，石蜡包埋组织的储存时间与AVP - mRNA的总量之间存在显著的正相关。在PVN中存在显著的正相关，但在SON中不存在，脑脊液的pH值（一种濒死状态的标志物）与AVP mRNA的总量之间存在显著的正相关。SON和PVN中目前AVP - mRNA水平未发生变化，这证实了早期关于这些核在衰老和AD过程中细胞数量稳定性的观察结果。尽管基于其他参数预期会出现AVP - mRNA上调，但长时间的逐渐慢性刺激可能会诱导替代的调节机制，如翻译能力或mRNA稳定性的变化。
