Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
J Neuroimmunol. 2011 Apr;233(1-2):54-64. doi: 10.1016/j.jneuroim.2010.11.012. Epub 2010 Dec 24.
Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation. The purpose of this study was to investigate sympathetic innervation of lymphoid organs and associated alterations in immune responses in young and aging female Fischer 344 (F344) rats. Histofluorescence and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old (onset of irregular estrous cycling), and 24-25 month, and 30-31 month female F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production, T and B lymphocyte proliferation were examined in splenocytes. Sympathetic NA innervation and NE levels increased with aging in the thymus, declined in spleen and MLN, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-γ production, and T and B cell proliferation in old female rats. In 8-9 mo rats, NE levels in the hilar region of the spleen and IFN-γ production were unaltered, while NE levels in the end region of the spleen and IL-2 production were reduced. Collectively, these results suggest that aging is characterized by significant alterations in sympathetic NA innervation in the thymus, spleen, and MLN associated with immunosuppression, and that there is a marked shift in NA activity and immune reactivity occurring during middle-aged female rats.
正常的衰老过程以及心理压力都会影响免疫系统；它们可以单独作用，也可以相互作用，导致免疫功能失调，极大地改变身心健康。交感神经系统（SNS）是应激对免疫功能影响的主要介导者，它受到正常衰老过程的显著影响，而应激也会影响 SNS 的衰老。此前，我们已经观察到雄性啮齿动物的淋巴器官交感去甲肾上腺素（NA）神经支配与年龄相关的变化，这些变化会影响免疫调节。本研究的目的是研究年轻和衰老雌性 Fischer 344（F344）大鼠的淋巴器官交感神经支配及其对免疫反应的相关改变。我们对 3 个月大的年轻（正常动情周期）、8-9 个月大（不规则动情周期开始）、24-25 个月大和 30-31 个月大（无动情周期）的雌性 F344 大鼠的胸腺、脾和肠系膜淋巴结（MLN）进行组织荧光和 NA 神经支配免疫细胞化学以及去甲肾上腺素（NE）水平的神经化学分析，基于阴道涂片确定动情周期。我们还研究了脾细胞中自然杀伤（NK）细胞活性、白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）产生、T 和 B 淋巴细胞增殖的年龄相关性变化。随着年龄的增长，胸腺中的交感 NA 神经支配和 NE 水平增加，脾和 MLN 中的交感 NA 神经支配和 NE 水平下降，同时 NK 细胞活性、IL-2 和 IFN-γ产生以及 T 和 B 细胞增殖显著减少，这表明老年雌性大鼠存在明显的免疫抑制。在 8-9 个月大的大鼠中，脾门区的 NE 水平和 IFN-γ产生没有改变，而脾尾区的 NE 水平和 IL-2 产生减少。总的来说，这些结果表明，衰老的特征是胸腺、脾和 MLN 中的交感 NA 神经支配发生显著变化，与免疫抑制有关，并且在中年雌性大鼠中存在显著的 NA 活性和免疫反应转移。
