González Iván, Arévalo-Serrano Juan, Sanz-Anquela José Miguel, Gonzalo-Ruiz Alicia
Laboratory of Neuroanatomy, Institute of Neuroscience of Castilla and León, University of Valladolid, Campus de los Pajaritos de Soria, 42004 Soria, Spain.
Acta Neuropathol. 2007 Jun;113(6):637-51. doi: 10.1007/s00401-007-0201-1. Epub 2007 Feb 9.
Cortical cholinergic dysfunction has been correlated with the expression and processing of beta-amyloid precursor protein. However, it remains unclear as to how cholinergic dysfunction and beta-amyloid (Abeta) formation and deposition might be related to one another. Since the M1- and M2 subtypes of muscarinic acetylcholine receptors (mAChRs) are considered key molecules that transduce the cholinergic message, the purpose of the present study was to assess the effects of the injected Abeta peptide on the number of M1mAchR- and M2mAChR-immunoreactive cells in the medial septum-diagonal band (MS-nDBB) complex of the rat. Injections of Abeta protein into the retrosplenial cortex resulted in a decrease in M1mAChR and M2mAChR immunoreactivity in the MS-nDBB complex. Quantitative analysis revealed a significant reduction in the number of M1mAChR- and M2mAChR-immunoreactive cells in the medial septum nucleus (MS) and in the horizontal nucleus of the diagonal band of Broca (HDB) as compared to the corresponding hemisphere in control animals and with that seen in the contralateral hemisphere, which corresponds to the PBS-injected side. Co-localization studies showed that the M1mAChR protein is localized in GABA-immunoreactive cells of the MS-nDBB complex, in particular those of the MS nucleus, while M2mAChR protein is localized in both the cholinergic and GABAergic cells. Moreover, GABAergic cells containing M2mAChR are mainly localized in the MS nucleus, while cholinergic cells containing M2mAChR are localized in the MS and the HDB nuclei. Our findings suggest that Abeta induces a reduction in M1mAChR- and M2mAChR-containing cells, which may contribute to impairments of cholinergic and GABAergic transmission in the MS-nDBB complex.
皮质胆碱能功能障碍与β-淀粉样前体蛋白的表达及加工过程相关。然而，胆碱能功能障碍与β-淀粉样蛋白（Aβ）的形成和沉积之间究竟如何相互关联仍不清楚。由于毒蕈碱型乙酰胆碱受体（mAChRs）的M1和M2亚型被认为是传递胆碱能信息的关键分子，本研究旨在评估注射Aβ肽对大鼠内侧隔-斜角带（MS-nDBB）复合体中M1mAChR和M2mAChR免疫反应性细胞数量的影响。向大鼠脾后皮质注射Aβ蛋白会导致MS-nDBB复合体中M1mAChR和M2mAChR免疫反应性降低。定量分析显示，与对照动物相应半球以及对侧半球（即注射PBS的一侧）相比，内侧隔核（MS）和布罗卡斜角带水平核（HDB）中M1mAChR和M2mAChR免疫反应性细胞数量显著减少。共定位研究表明，M1mAChR蛋白定位于MS-nDBB复合体的GABA免疫反应性细胞中，尤其是MS核的细胞，而M2mAChR蛋白则定位于胆碱能和GABA能细胞中。此外，含有M2mAChR的GABA能细胞主要定位于MS核，而含有M2mAChR的胆碱能细胞则定位于MS核和HDB核。我们的研究结果表明，Aβ可诱导含有M1mAChR和M2mAChR的细胞数量减少，这可能导致MS-nDBB复合体中胆碱能和GABA能传递受损。
