Ferretti C, Blengio M, Ghi P, Adage T, Portaleone P, Ricci Gamalero S
Dipartimento di Anatomia, Farmacologia e Medicina Legale, Universita' di Torino, Italy.
Pharmacol Biochem Behav. 1998 Jan;59(1):255-60. doi: 10.1016/s0091-3057(97)00395-x.
Changes in the baseline and in the 40 mM K+-evoked release of histamine from hypothalamus slices were compared in male and female rats aged 2, 6, 12, 18, and 24 months. The baseline release declined in the 12-, 18-, and 24-month males. In contrast, the K+-evoked release remained constant in the males, but in the females it decreased in animals more than 2 months old. The efficiency of the H3 receptors was also determined by measuring the reduction of the K+-evoked release induced by the H3 receptor agonist (R)-alpha-methylhistamine. This substance significantly decreased the amount of HA released in all age groups, except the 24-month-old males. Histamine release was also measured after exposure to a weak electrical stress. In 2- and 6-month-old males, there was a marked reduction of both the baseline and the K+-evoked release, and also of the inhibitory effect of the H3 agonist. There were no changes in the 12- and 18-month age groups, but both releases were enhanced in the 24-month group. In females, electrical stress had no significant effect, except in the youngest age group. Stress-dependent release of plasma corticosterone was decreased in males older than 12 months and in females older than 6 months. These changes gave a good correlation with variation in the H3 receptors. This study, therefore, demonstrates that aging modifies, in a sex-dependent way, the basal and stress-stimulated functions of the hypothalamic presynaptic histaminergic neurons.
比较了2、6、12、18和24月龄雄性和雌性大鼠下丘脑切片中组胺的基础释放量以及40 mM钾离子诱发的释放量的变化。12、18和24月龄雄性大鼠的基础释放量下降。相比之下，雄性大鼠中钾离子诱发的释放量保持不变，但在2月龄以上的雌性大鼠中，该释放量减少。还通过测量H3受体激动剂（R）-α-甲基组胺诱导的钾离子诱发释放量的减少来确定H3受体的效率。除24月龄雄性大鼠外，该物质在所有年龄组中均显著降低了组胺释放量。在施加弱电应激后也测量了组胺释放量。在2和6月龄雄性大鼠中，基础释放量、钾离子诱发的释放量以及H3激动剂的抑制作用均显著降低。12和18月龄组没有变化，但24月龄组的两种释放量均增加。在雌性大鼠中，除最年幼的年龄组外，电应激没有显著影响。12月龄以上的雄性大鼠和6月龄以上的雌性大鼠中，应激依赖性血浆皮质酮的释放量降低。这些变化与H3受体的变化有很好的相关性。因此，本研究表明，衰老以性别依赖的方式改变了下丘脑突触前组胺能神经元的基础功能和应激刺激功能。
