Lemke R, Härtig W, Rossner S, Bigl V, Schliebs R
Paul Flechsig Institute for Brain Research, University of Leipzig, Medical Faculty, Germany.
J Neurosci Res. 1998 Jan 15;51(2):223-36. doi: 10.1002/(SICI)1097-4547(19980115)51:2<223::AID-JNR11>3.0.CO;2-9.
Interleukin-6 may play an essential role in early inflammatory processes as response to degenerating cholinergic cells in the nucleus basalis of Meynert in patients suffering Alzheimer's disease. The cholinergic immunotoxin, 192IgG-saporin, was applied to produce selective and specific degenerations of basal forebrain cholinergic cells. To disclose the lesion-induced temporal cascade of the expression pattern of IL-6, and to reveal the cellular source for production and secretion of IL-6 in vivo after endogeneously induced basal forebrain cholinergic cell loss, both in situ hybridization and immunocytochemistry for IL-6 were performed. To identify the cell types expressing IL-6 mRNA, double labeling techniques were applied combining in situ hybridization technique with immunocytochemistry and lectin histochemistry for both micro- and astroglia and a number of neuronal markers including choline acetyltransferase, parvalbumin, and neurofilaments. In the intact brain, IL-6 is mainly localized in neurons, in particular in both cholinergic and GABAergic neurons of the basal forebrain. Although basal forebrain cholinergic lesion resulted in a dramatic increase in the number of micro- and astroglial cells at the lesion site, IL-6 expression could not be detected in any of the lesion-induced activated glial cell types. Moreover, cholinergic lesion led to a reduced number of IL-6-expressing cells in the basal forebrain, which is assumed to be due to the loss of cholinergic cells. The predominantly neuronal localization in rat brain suggests a role for IL-6 in activating micro- and astroglial cells in response to degenerating cholinergic neurons.
白细胞介素-6可能在早期炎症过程中发挥重要作用，这是对阿尔茨海默病患者中脑基底核退化胆碱能细胞的一种反应。应用胆碱能免疫毒素192IgG-皂草素，以产生基底前脑胆碱能细胞的选择性和特异性退化。为了揭示损伤诱导的白细胞介素-6表达模式的时间级联反应，并揭示内源性诱导基底前脑胆碱能细胞丢失后体内白细胞介素-6产生和分泌的细胞来源，进行了白细胞介素-6的原位杂交和免疫细胞化学研究。为了识别表达白细胞介素-6 mRNA的细胞类型，应用了双重标记技术，将原位杂交技术与免疫细胞化学以及针对小胶质细胞和星形胶质细胞以及包括胆碱乙酰转移酶、小白蛋白和神经丝在内的多种神经元标志物的凝集素组织化学相结合。在完整的大脑中，白细胞介素-6主要定位于神经元，特别是基底前脑的胆碱能和γ-氨基丁酸能神经元。尽管基底前脑胆碱能损伤导致损伤部位的小胶质细胞和星形胶质细胞数量急剧增加，但在任何损伤诱导的活化胶质细胞类型中均未检测到白细胞介素-6的表达。此外，胆碱能损伤导致基底前脑中表达白细胞介素-6的细胞数量减少，这被认为是由于胆碱能细胞的丢失所致。大鼠脑中白细胞介素-6主要定位于神经元，这表明白细胞介素-6在响应退化的胆碱能神经元激活小胶质细胞和星形胶质细胞方面发挥作用。
