Cardinali D P, Brusco L I, Selgas L, Esquifino A I
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, CC 243, 1425 Buenos Aires, Argentina.
Brain Res. 1998 Apr 13;789(2):283-92. doi: 10.1016/s0006-8993(98)00015-8.
Aging has been associated with attenuation of amplitude and changes in period of many circadian rhythms. The present study was carried out to examine, in young (50 days old) and old (18 months old) rats, whether 24-h rhythms of cell proliferation (as assessed by measuring ornithine decarboxylase activity) and of presynaptic adrenergic and cholinergic markers change in lymph nodes and spleen during Freund's adjuvant-induced arthritis. Groups of young and old Sprague-Dawley rats were studied the day before, and on days 6, 12 and 18 after Freund's adjuvant injection. On day 16 after adjuvant injection, inflammation of hind paws, mainly in the ankle joints, was less marked in old than in young rats. Lymph node and splenic ornithine decarboxylase activity exhibited significant 24-h variations with maximal activity during daily hours. Before treatment, enzyme activity values were significantly lower in old rats in both tissues examined. During the immune reaction, lymph node and splenic ornithine decarboxylase augmented 8-10-fold, with progressively smaller amplitude of daily variations as arthritis developed. In every case, mesor and amplitude of ornithine decarboxylase activity were lowest in old rats. Submaxillary lymph node and splenic tyrosine hydroxylase activity attained maximal values at night. At every time interval after mycobacterium adjuvant injection, amplitude and mesor of tyrosine hydroxylase activity rhythm were lowest in old rats. A maximum in submaxillary lymph node 3H-acetylcholine synthesis occurred at the afternoon. On day 6 and 12 after Freund's adjuvant injection, lymph node 3H-acetylcholine synthesis was significantly smaller in old rats. Day-night differences in submaxillary lymph node or splenic ornithine decarboxylase and tyrosine hydroxylase activities, or in submaxillary lymph node 3H-acetylcholine synthesis, of rats treated with the adjuvant's vehicle, did not differ significantly from those seen in untreated controls. The results are compatible with an age-dependent decline of immune-mediated inflammatory responses. The activity of the central circadian oscillator, driven to the organs in part via the autonomic nervous system, seems also to deteriorate during aging.
衰老与许多昼夜节律的振幅衰减和周期变化有关。本研究旨在检测在弗氏佐剂诱导的关节炎期间，年轻（50日龄）和年老（18月龄）大鼠淋巴结和脾脏中细胞增殖的24小时节律（通过测量鸟氨酸脱羧酶活性评估）以及突触前肾上腺素能和胆碱能标志物是否发生变化。在弗氏佐剂注射前一天以及注射后第6、12和18天对年轻和年老的斯普拉格-道利大鼠组进行研究。在佐剂注射后第16天，年老大鼠后爪（主要是踝关节）的炎症比年轻大鼠轻。淋巴结和脾脏鸟氨酸脱羧酶活性呈现显著的24小时变化，在一天中的特定时段活性最高。治疗前，在所检测的两种组织中，年老大鼠的酶活性值均显著较低。在免疫反应期间，随着关节炎的发展，淋巴结和脾脏鸟氨酸脱羧酶增加8 - 10倍，每日变化幅度逐渐减小。在每种情况下，年老大鼠鸟氨酸脱羧酶活性的中值和振幅最低。颌下淋巴结和脾脏酪氨酸羟化酶活性在夜间达到最大值。在注射分枝杆菌佐剂后的每个时间间隔，年老大鼠酪氨酸羟化酶活性节律的振幅和中值最低。颌下淋巴结3H - 乙酰胆碱合成在下午达到最大值。在弗氏佐剂注射后第6天和第12天，年老大鼠的淋巴结3H - 乙酰胆碱合成显著减少。用佐剂载体处理的大鼠，其颌下淋巴结或脾脏鸟氨酸脱羧酶和酪氨酸羟化酶活性，或颌下淋巴结3H - 乙酰胆碱合成的昼夜差异与未处理对照组相比无显著差异。结果表明免疫介导的炎症反应存在年龄依赖性下降。部分通过自主神经系统驱动至器官的中枢昼夜节律振荡器的活性在衰老过程中似乎也会恶化。
