Madl J E, Duncan C G, Stanhill J E, Tai P-Y, Spraker T R, Gulland F M
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
J Comp Pathol. 2014 Feb-Apr;150(2-3):306-15. doi: 10.1016/j.jcpa.2013.07.012. Epub 2013 Sep 21.
The aim of this study was to test the hypothesis that oxidative stress and glutamine synthetase (GS) redistribution occur in domoic acid (DA) toxicosis in California sea lions (CSLs, Zalophus californianus). Sections of archived hippocampi from seven control and 13 CSLs diagnosed with DA toxicosis were labelled immunohistochemically for GS and for two markers of oxidative stress, malondialdehyde (MDA) and 3-nitrotyrosine (NT). The distribution and intensity of labelling were compared with the pathological changes seen in haematoxylin and eosin-stained sections. Increased expression of MDA and NT occurred in neurons of the hippocampal formation of CSLs with lesions consistent with DA toxicosis. The degree of oxidative stress was not affected significantly by the chronicity or severity of hippocampal damage. In six out of seven CSLs with chronic effects of DA toxicosis, in addition to the normal glial distribution of GS, GS expression was very strong in some neurons of the subiculum. However, neuronal GS labelling was also seen in one control CSL, an effect that may have been due to previous exposure to DA. GS expression in neurons was associated with decreases in GS labelling in neighbouring glial cell processes. DA toxicosis therefore induces increased expression of markers of oxidative stress in neurons consistent with oxidative stress contributing to the initial DA insult and also the epilepsy that often develops in chronic DA toxicosis. GS redistribution occurred primarily in chronic DA toxicosis, perhaps leading to alterations of the glutamine-glutamate-GABA (gamma-aminobutyric acid) cycle and contributing to the excitotoxicity and seizures often seen in DA toxicosis.
在加利福尼亚海狮（CSLs，北海狮属）的软骨藻酸（DA）中毒中会发生氧化应激和谷氨酰胺合成酶（GS）重新分布。对7只对照海狮和13只被诊断为DA中毒的CSLs的存档海马体切片进行免疫组织化学标记以检测GS以及氧化应激的两个标志物丙二醛（MDA）和3-硝基酪氨酸（NT）。将标记的分布和强度与苏木精-伊红染色切片中所见的病理变化进行比较。在患有与DA中毒一致病变的CSLs海马结构的神经元中，MDA和NT的表达增加。氧化应激程度不受海马损伤的慢性程度或严重程度的显著影响。在7只具有DA中毒慢性影响的CSLs中，有6只除了GS在胶质细胞中的正常分布外，在海马下托的一些神经元中GS表达也非常强。然而，在一只对照CSL中也观察到神经元GS标记，这种效应可能是由于先前接触过DA。神经元中的GS表达与相邻胶质细胞突起中GS标记的减少有关。因此，DA中毒会诱导神经元中氧化应激标志物的表达增加，这与氧化应激导致最初的DA损伤以及慢性DA中毒中经常发生的癫痫有关。GS重新分布主要发生在慢性DA中毒中，这可能导致谷氨酰胺-谷氨酸-γ-氨基丁酸（GABA）循环的改变，并导致DA中毒中常见的兴奋性毒性和癫痫发作。
