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哺乳动物脑内低剂量辐射后 pTau 和 APP 水平降低。

Reduction of pTau and APP levels in mammalian brain after low-dose radiation.

机构信息

DoD/USU Brain Tissue Repository and Neuropathology Core, Uniformed Services University (USU), Bethesda, MD, USA.

Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA.

出版信息

Sci Rep. 2021 Jan 26;11(1):2215. doi: 10.1038/s41598-021-81602-z.

Abstract

Brain radiation can occur from treatment of brain tumors or accidental exposures. Brain radiation has been rarely considered, though, as a possible tool to alter protein levels involved in neurodegenerative disorders. We analyzed possible molecular and neuropathology changes of phosphorylated-Tau (pTau), all-Tau forms, β-tubulin, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), myelin basic protein (MBP), and GAP43 in Frontal Cortex (FC), Hippocampus (H) and Cerebellum (CRB) of swine brains following total-body low-dose radiation (1.79 Gy). Our data show that radiated-animals had lower levels of pTau in FC and H, APP in H and CRB, GAP43 in CRB, and higher level of GFAP in H versus sham-animals. These molecular changes were not accompanied by obvious neurohistological changes, except for astrogliosis in the H. These findings are novel, and might open new perspectives on brain radiation as a potential tool to interfere with the accumulation of specific proteins linked to the pathogenesis of various neurodegenerative disorders.

摘要

脑辐射可源于脑瘤治疗或意外暴露。然而,脑辐射作为一种改变神经退行性疾病相关蛋白水平的可能手段,却很少被考虑。我们分析了猪脑全脑低剂量辐射(1.79 Gy)后,额皮质(FC)、海马(H)和小脑(CRB)中磷酸化 Tau(pTau)、总 Tau 形式、β-微管蛋白、淀粉样前体蛋白(APP)、神经胶质纤维酸性蛋白(GFAP)、离子钙结合衔接分子 1(IBA-1)、髓鞘碱性蛋白(MBP)和 GAP43 的可能分子和神经病理学变化。我们的数据显示,辐射动物的 FC 和 H 中的 pTau、H 和 CRB 中的 APP、CRB 中的 GAP43 水平较低,而 H 中的 GFAP 水平较高,与假手术动物相比。这些分子变化没有伴随着明显的神经组织学变化,除了 H 中的星形胶质增生。这些发现是新颖的,可能为脑辐射作为一种潜在工具来干扰与各种神经退行性疾病发病机制相关的特定蛋白质积累开辟新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a735/7838187/1eca4d4b7cb0/41598_2021_81602_Fig1_HTML.jpg

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