Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709, Olsztyn, Poland.
Division of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. Oczapowskiego 13, 10-950, Olsztyn, Poland.
Neurotox Res. 2019 Jan;35(1):29-40. doi: 10.1007/s12640-018-9920-4. Epub 2018 Jun 7.
Microcystin-LR (MC-LR) is a potent hepatotoxin that has also been pointed out of causing neurotoxicity, but the exact mechanisms of action still remain ambiguous and need to be elucidated. Data from studies on mammals show that pathology of astrocyte cells points to perturbations of microRNA signaling. Glial fibrillary acidic protein (GFAP), a neuronal cell/astrocyte-specific protein, and a microRNA-124-3p (MiR124-3p) are among putative triggers and regulators of neuronal cell/astrocyte reactivity. In the present study on whitefish (Coregonus lavaretus), we found that gfap mRNA contains a putative target site for MIR124-3p, to potentially affect its expression changes. qPCR expression study of gfap:MiR124-3p pair in the midbrain of juvenile whitefish, during 28 days of exposure to a repeated subacute dose of MC-LR (100 μg kg body mass), showed marginally significant up-regulation of gfap only on the 7th day of exposure period which suggests neuronal toxicity. During the whole exposure period, neither midbrain nor blood plasma levels of MiR124-3p were changed. Furthermore, double luciferase gene reporter assay confirmed the lack of MiR124-3p involvement in mediating control over gfap mRNA expression. These data show that, although MC-LR may trigger neuronal toxicity in whitefish, this does not involve MiR124-3p in response to the treatment.
微囊藻毒素-LR（MC-LR）是一种有效的肝毒素，也被指出具有神经毒性，但确切的作用机制仍不清楚，需要进一步阐明。来自哺乳动物研究的数据表明，星形胶质细胞的病理学表明微小 RNA 信号的扰动。神经胶质原纤维酸性蛋白（GFAP）是神经元/星形胶质细胞特异性蛋白，microRNA-124-3p（MiR124-3p）是神经元/星形胶质细胞反应的潜在触发因子和调节因子之一。在本研究中，我们在白鲑鱼（Coregonus lavaretus）中发现，gfap mRNA 含有 MIR124-3p 的潜在靶位点，可能影响其表达变化。在暴露于重复亚急性剂量 MC-LR（100μgkg 体重）的 28 天期间，对幼白鲑鱼中脑的 gfap:MiR124-3p 对进行 qPCR 表达研究，仅在暴露期的第 7 天发现 gfap 表达呈轻微显著上调，表明存在神经毒性。在整个暴露期内，中脑和血浆 MiR124-3p 水平均未发生变化。此外，双荧光素酶基因报告基因检测证实 MiR124-3p 缺乏参与介导 gfap mRNA 表达的控制。这些数据表明，尽管 MC-LR 可能在白鲑鱼中引发神经毒性，但这与 MiR124-3p 对治疗的反应无关。
