Madden K S, Bellinger D L, Felten S Y, Snyder E, Maida M E, Felten D L
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Mech Ageing Dev. 1997 Mar;94(1-3):165-75. doi: 10.1016/s0047-6374(96)01858-1.
Age is associated with reduced immune reactivity, contributing to increased rates of infectious disease and cancer in old age. We have begun to assess the potential for sympathetic nervous system involvement in age-related immune dysfunction by characterizing sympathetic noradrenergic (NA) innervation in lymphoid organs in old animals. In the present study noradrenergic innervation of spleen and thymus was examined histologically and neurochemically in 2-, 12- and 24-month old BALB/c mice. In the thymus of 2-month old animals, NA nerve fibers were found in the subcapsular, cortical, and cortico-medullary regions associated with blood vessels and septa; occasional branches from these nerve fibers entered the parenchyma. With increasing age and thymic involution, NA nerve fibers increased in density; by 24 months of age, dense plexuses were compacted among septa and blood vessels, and numerous linear, varicose nerve fibers were observed branching into the parenchyma. Thymic norepinephrine (NE) concentration (per mg wet weight) increased approximately 4-fold in 12-month old animals and 15-fold in 24-month old animals. Taking the reduced thymus weight into account, total thymic NE at 12- and 24-month of age was equivalent to total thymic NE at 2-month of age, suggesting that NA innervation is maintained as the thymus involutes. In the spleen from 2-month old animals, NA innervation entered the white pulp with the central artery to innervate the periarteriolar lymphatic sheath and the marginal zone. At 12-month of age, histologically and neurochemically there was no change in splenic NA innervation. By 24-month of age, NE was increased significantly, independent of changes in spleen weight. Histologically, increased catecholamine-containing fibers were apparent at 24-month of age, particularly in the parenchyma surrounding the central artery. The alterations in sympathetic NA innervation of lymphoid organs with age suggest that the sympathetic nervous system and NE may play a role in age-associated immune dysregulation. Alternatively, the changes in NA innervation may be secondary to functional changes within the immune system.
年龄与免疫反应性降低相关，这导致老年时传染病和癌症的发病率增加。我们已开始通过表征老年动物淋巴器官中的交感去甲肾上腺素能（NA）神经支配，来评估交感神经系统参与与年龄相关的免疫功能障碍的可能性。在本研究中，对2个月、12个月和24个月大的BALB/c小鼠的脾脏和胸腺的去甲肾上腺素能神经支配进行了组织学和神经化学检查。在2个月大的动物胸腺中，NA神经纤维存在于与血管和间隔相关的被膜下、皮质和皮质髓质区域；这些神经纤维偶尔的分支进入实质。随着年龄增长和胸腺退化，NA神经纤维密度增加；到24个月大时，密集的神经丛在间隔和血管之间紧密排列，并且观察到许多线性、曲张的神经纤维分支进入实质。胸腺去甲肾上腺素（NE）浓度（每毫克湿重）在12个月大的动物中增加了约4倍，在24个月大的动物中增加了15倍。考虑到胸腺重量的减轻，12个月和24个月大时胸腺NE总量与2个月大时胸腺NE总量相当，这表明随着胸腺退化，NA神经支配得以维持。在2个月大的动物脾脏中，NA神经支配随着中央动脉进入白髓，以支配动脉周围淋巴鞘和边缘区。在12个月大时，脾脏NA神经支配在组织学和神经化学上没有变化。到24个月大时，NE显著增加，与脾脏重量变化无关。在组织学上，含儿茶酚胺纤维在24个月大时明显增加，特别是在中央动脉周围的实质中。淋巴器官中交感NA神经支配随年龄的变化表明，交感神经系统和NE可能在与年龄相关的免疫失调中起作用。或者，NA神经支配的变化可能是免疫系统内功能变化的继发结果。
