Neuroscience Research Australia, Randwick, Australia.
School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Brain Pathol. 2019 Nov;29(6):813-825. doi: 10.1111/bpa.12730. Epub 2019 Jun 14.
Growth factors can facilitate hippocampus-based learning and memory and are potential targets for treatment of cognitive dysfunction via their neuroprotective and neurorestorative effects. Dementia is common in Parkinson's disease (PD), but treatment options are limited. We aimed to determine if levels of growth factors are altered in the hippocampus of patients with PD, and if such alterations are associated with PD pathology. Enzyme-linked immunosorbent assays were used to quantify seven growth factors in fresh frozen hippocampus from 10 PD and nine age-matched control brains. Western blotting and immunohistochemistry were used to explore cellular and inflammatory changes that may be associated with growth factor alterations. In the PD hippocampus, protein levels of glial cell line-derived neurotrophic factor were significantly decreased, despite no evidence of neuronal loss. In contrast, protein levels of fibroblast growth factor 2 and cerebral dopamine neurotrophic factor were significantly increased in PD compared to controls. Levels of the growth factors epidermal growth factor, heparin-binding epidermal growth factor, brain-derived neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor did not differ between groups. Our data demonstrate changes in specific growth factors in the hippocampus of the PD brain, which potentially represent targets for modification to help attenuate cognitive decline in PD. These data also suggest that multiple growth factors and direction of change needs to be considered when approaching growth factors as a potential treatment for cognitive decline.
生长因子可以促进海马体相关的学习和记忆,通过其神经保护和神经修复作用,成为治疗认知功能障碍的潜在靶点。痴呆在帕金森病(PD)中很常见,但治疗选择有限。我们旨在确定 PD 患者海马体中的生长因子水平是否发生改变,以及这种改变是否与 PD 病理相关。采用酶联免疫吸附试验(ELISA)定量分析 10 例 PD 和 9 例年龄匹配的对照脑新鲜冷冻海马体中的 7 种生长因子。Western blot 和免疫组织化学用于探索可能与生长因子改变相关的细胞和炎症变化。在 PD 海马体中,神经胶质细胞源性神经营养因子的蛋白水平显著降低,尽管没有神经元丢失的证据。相比之下,与对照组相比,成纤维细胞生长因子 2 和脑多巴胺神经营养因子的蛋白水平在 PD 中显著增加。表皮生长因子、肝素结合表皮生长因子、脑源性神经营养因子和中脑星形胶质细胞源性神经营养因子的水平在两组之间没有差异。我们的数据表明,PD 大脑海马体中特定生长因子发生变化,这些因子可能成为改变以帮助减轻 PD 认知衰退的目标。这些数据还表明,在将生长因子作为认知衰退的潜在治疗方法时,需要考虑多种生长因子和变化方向。