Hastings J A, McClure-Sharp J M, Morris M J
School of Biological and Chemical Sciences, Deakin University, Victoria, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):218-24. doi: 10.1007/pl00005160.
Marked changes in brain monoamine content and NPY content occur during maturation and ageing. Earlier in vivo studies in our laboratory have reported blunted K+ stimulated noradrenaline release and reduced NPY overflow in aged animals using microdialysis and push pull techniques. In this study, in vitro superfusion techniques were established to measure endogenous noradrenaline, NPY, DOPAC and 5-HIAA overflow from the hypothalamus of 1, 5 and 16 month old Sprague-Dawley rats. A period of high K+ (56 mM) stimulation was carried out to elicit maximal release. Basal noradrenaline overflow was similar in all age groups of rats and during K+-induced depolarisation similar 3-4 fold increases were observed. On the other hand, basal and K+ stimulated NPY overflow were significantly greater in the adult rats compared to 1 month and 16 month old rats. Despite differences in absolute NPY overflow, the relative increase over resting was not significantly different across age groups. The molar quantities of hypothalamic NPY overflow at rest and under K+ stimulated conditions were three orders of magnitude lower than noradrenaline. Results of these studies suggest that both NPY and noradrenaline can be released from a similar hypothalamic pool. Basal and K+-evoked DOPAC and 5-HIAA overflow were similar between the 3 age groups. Thus the overflow of hypothalamic noradrenaline, DOPAC and 5-HIAA under in vitro conditions was not altered from 1 to 16 months. In contrast, 5 month old rats had significantly higher NPY overflow than the other age groups (P < 0.05), consistent with a reported decline in NPY content with advanced age. Hypothalamic noradrenaline overflow was not affected by ageing, suggesting that a selective loss of NPY in the arcuo-PVN projection, or other projections to the hypothalamus with ageing may contribute to the reduction in NPY overflow in aged rats.
在成熟和衰老过程中，脑内单胺含量和神经肽Y（NPY）含量会发生显著变化。我们实验室早期的体内研究报告称，使用微透析和推挽技术，在老年动物中，钾离子（K⁺）刺激的去甲肾上腺素释放减弱，NPY溢出减少。在本研究中，建立了体外灌流技术，以测量1月龄、5月龄和16月龄Sprague-Dawley大鼠下丘脑内源性去甲肾上腺素、NPY、3,4-二羟基苯乙酸（DOPAC）和5-羟吲哚乙酸（5-HIAA）的溢出情况。进行了一段高钾（56 mM）刺激期以引发最大释放。所有年龄组大鼠的基础去甲肾上腺素溢出相似，在钾离子诱导的去极化过程中，观察到相似的3-4倍增加。另一方面，与1月龄和16月龄大鼠相比，成年大鼠的基础和钾离子刺激的NPY溢出显著更高。尽管绝对NPY溢出存在差异，但各年龄组静息时的相对增加并无显著差异。在静息和钾离子刺激条件下，下丘脑NPY溢出的摩尔量比去甲肾上腺素低三个数量级。这些研究结果表明，NPY和去甲肾上腺素都可以从相似的下丘脑池中释放出来。三个年龄组之间基础和钾离子诱发的DOPAC和5-HIAA溢出相似。因此，体外条件下下丘脑去甲肾上腺素、DOPAC和5-HIAA的溢出在1至16个月内没有改变。相比之下，5月龄大鼠的NPY溢出显著高于其他年龄组（P < 0.05），这与报道的随着年龄增长NPY含量下降一致。下丘脑去甲肾上腺素溢出不受衰老影响，这表明随着年龄增长，弓状核-室旁核投射或其他下丘脑投射中NPY的选择性丢失可能导致老年大鼠NPY溢出减少。
