Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine No. 600 South Wanping Road, Shanghai 200080, China.
Neuroscience. 2011 Jun 16;184:151-63. doi: 10.1016/j.neuroscience.2011.03.059. Epub 2011 Apr 7.
Bone morphogenetic protein 7 (BMP7) has neuroprotective effects against ischemia, oxidation stress, and lipopolysaccharide, but its role on amyloid-beta (Aβ)-induced neurotoxicity in Alzheimer's disease (AD) and the underlying mechanisms remain unclear. In this study, we exposed PC12 cells to Aβ25-35 for 26 h to induce neurotoxicity, and added exogenous BMP7 at 2 h to observe the neuroprotective effects. The protective mechanisms involved, mostly related to inhibition of cell apoptosis and oxidation stress, were analyzed. In rat in vivo experiments, we bilaterally injected Aβ1-40 into the basal forebrain to simulate neuropathological processes in AD, performed the Morris water maze test to evaluate the effect of Aβ on spatial learning and memory, and explored the change of endogenous BMP7 expression in the brain. The present study demonstrated that BMP7 prevented neuronal injuries in PC12 cells induced by Aβ25-35, including cell apoptosis and morphological impairment of dendrites as well as oxidation stress. BMP7 treatment significantly protected PC12 cells against Aβ25-35-induced injury and inhibited the increasing content of the Bax gene and the decreasing activities of superoxide dismutase (SOD). Aβ1-40 bilaterally injected into the rat basal forebrain obviously inhibited the rat's spatial learning ability and memory, and significantly induced downregulation of endogenous BMP7 in the basal forebrain while upregulating it in the hippocampus. Our results suggest that BMP7 has neuroprotective effects against Aβ, which may be mediated through inhibition of Bax gene expression during cell apoptosis and elevation of SOD activities during the oxidative stress response. On the other hand, endogenous BMP7 may have a potential self-modulation capacity through negative feedback between the region of the basal forebrain and the hippocampus as a protective cytokine.
骨形态发生蛋白 7（BMP7）对缺血、氧化应激和脂多糖具有神经保护作用，但它在阿尔茨海默病（AD）中对淀粉样β（Aβ）诱导的神经毒性的作用及其潜在机制尚不清楚。在这项研究中，我们将 PC12 细胞暴露于 Aβ25-35 中 26 小时以诱导神经毒性，并在 2 小时时添加外源性 BMP7 以观察神经保护作用。分析了涉及的保护机制，主要与抑制细胞凋亡和氧化应激有关。在大鼠体内实验中，我们将 Aβ1-40 双侧注射到基底前脑以模拟 AD 的神经病理学过程，进行 Morris 水迷宫测试以评估 Aβ对空间学习和记忆的影响，并探讨脑内内源性 BMP7 表达的变化。本研究表明，BMP7 可防止 Aβ25-35 诱导的 PC12 细胞损伤，包括细胞凋亡和树突形态损伤以及氧化应激。BMP7 处理可显著保护 PC12 细胞免受 Aβ25-35 诱导的损伤，并抑制 Bax 基因含量的增加和超氧化物歧化酶（SOD）活性的降低。Aβ1-40 双侧注射到大鼠基底前脑明显抑制了大鼠的空间学习能力和记忆，并明显诱导了基底前脑内源性 BMP7 的下调，同时上调了海马内源性 BMP7 的表达。我们的结果表明，BMP7 对 Aβ 具有神经保护作用，这可能是通过抑制细胞凋亡过程中的 Bax 基因表达和氧化应激反应中的 SOD 活性升高来介导的。另一方面，内源性 BMP7 可能通过基底前脑和海马区之间的负反馈具有潜在的自我调节能力，作为一种保护性细胞因子。
