Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease
Levels of glial cell line-derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson's disease
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DOI：
10.1111/bpa.12730
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发表时间：
2019-11-01
期刊：
影响因子：
6.4
通讯作者：
Double, Kay L.
中科院分区：
文献类型：
--
作者：
Virachit, Sophie;Mathews, Kathryn J.;Double, Kay L.
生长因子可以促进基于海马体的学习和记忆，并通过其神经保护和神经恢复作用成为治疗认知功能障碍的潜在靶点。痴呆症在帕金森氏病(PD)中很常见，但治疗选择有限。我们的目的是确定帕金森病患者海马区的生长因子水平是否发生了变化，以及这种变化是否与帕金森病的病理相关。采用酶联免疫吸附试验对10例帕金森病患者和9例年龄匹配的对照组脑组织新鲜冰冻海马区的7种生长因子进行了定量检测。Western blotting和免疫组织化学方法检测可能与生长因子改变相关的细胞和炎性改变。在PD海马区，胶质细胞源性神经营养因子的蛋白水平显著降低，尽管没有证据表明神经元丢失。相反，帕金森病患者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显著高于对照组。生长因子表皮生长因子、肝素结合性表皮生长因子、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水平在组间无差异。我们的数据显示了帕金森病大脑海马体中特定生长因子的变化，这些生长因子可能是修改的目标，以帮助减轻帕金森病患者的认知能力下降。这些数据还表明，在探讨生长因素作为认知衰退的潜在治疗方法时，需要考虑多种生长因素和变化方向。
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.