Wetmore L, Green-Johnson J, Gartner J G, Sanders V, Nance D M
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Brain Behav Immun. 1994 Dec;8(4):341-54. doi: 10.1006/brbi.1994.1031.
The lateral septal area (LSA) is a primary control region for psychoneuroendocrine functions, and we have previously reported that kainic acid (KA) lesions in the LSA and the hippocampus have inhibitory and facilitatory effects, respectively, on the humoral immune response of female rats. Thus, these limbic structures may selectively participate in directing neuroimmune regulation. In order to assess the fundamental role of the LSA in neuroimmune regulation, we have evaluated the effects of neurotoxic septal lesions on various cell-mediated immune measures. Animals received stereotaxically guided bilateral infusions of KA (2.0 micrograms/microliter) or physiological saline (SHAM) into the LSA. Following a 2-week recovery period, animals were sacrificed and the spleen cells analyzed for natural killer (NK) cell activity and T-cell responsiveness to mitogen (ConA) or to anti T-cell receptor mAb (R73). A separate group of LSA-lesioned animals were immunized with sheep red blood cells 4 days prior to harvesting the spleen for plaque forming cell (PFC) number determination and measurement of TNF-alpha secretion from splenic macrophages. The results indicate that rats with KA lesions in the LSA have significantly higher NK cell activity, significantly lower numbers of splenic PFCs, and significantly reduced TNF-alpha secretion from splenic macrophages, relative to controls. There was a statistical tendency (p < .1) for reduced T-cell lymphoproliferative responses to ConA stimulation in LSA-lesioned animals, relative to SHAMs. However, the T-cell lymphoproliferative response to specific activation via the T-cell receptor was not significantly different between lesioned and control groups. These results further demonstrate the importance of KA-sensitive LSA neurons in neuroimmunoregulation. Moreover, selective alterations of different components of the immune system are observed in LSA-lesioned animals, suggesting that the LSA is involved in the complex and differential regulation of immunity.
外侧隔区（LSA）是精神神经内分泌功能的主要控制区域，我们之前报道过，LSA和海马体中的海藻酸（KA）损伤分别对雌性大鼠的体液免疫反应具有抑制和促进作用。因此，这些边缘结构可能选择性地参与神经免疫调节的指导。为了评估LSA在神经免疫调节中的基本作用，我们评估了神经毒性隔区损伤对各种细胞介导免疫指标的影响。动物接受立体定位引导下向LSA双侧注入KA（2.0微克/微升）或生理盐水（假手术组）。经过2周的恢复期后，处死动物并分析脾细胞的自然杀伤（NK）细胞活性以及T细胞对丝裂原（刀豆蛋白A）或抗T细胞受体单克隆抗体（R73）的反应性。另一组LSA损伤动物在采集脾脏以测定斑块形成细胞（PFC）数量和测量脾巨噬细胞分泌的肿瘤坏死因子-α之前4天，用绵羊红细胞进行免疫。结果表明，与对照组相比，LSA中存在KA损伤的大鼠具有显著更高的NK细胞活性、显著更低的脾PFC数量以及显著减少的脾巨噬细胞肿瘤坏死因子-α分泌。相对于假手术组，LSA损伤动物对刀豆蛋白A刺激的T细胞淋巴细胞增殖反应有统计学上的降低趋势（p < 0.1）。然而，损伤组和对照组之间通过T细胞受体特异性激活的T细胞淋巴细胞增殖反应没有显著差异。这些结果进一步证明了KA敏感的LSA神经元在神经免疫调节中的重要性。此外，在LSA损伤动物中观察到免疫系统不同成分的选择性改变，表明LSA参与免疫的复杂和差异性调节。
