{"title":"Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation","authors":"","doi":"10.1016/j.bbr.2024.115219","DOIUrl":null,"url":null,"abstract":"<div><p>Our previous <em>in vitro</em> studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using <em>in vivo</em> and <em>in vitro</em> models. Thus, <em>in vivo</em> excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while <em>in vitro</em> spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166432824003759","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.
我们之前的体外研究表明,谷氨酸类似物凯恩酸盐(KA)诱发的兴奋毒性会显著减少大鼠脊髓神经元的数量,并引发谷氨酸的大量释放,导致运动网络阻滞。我们目前的目标是利用体内和体外模型评估 CREB 作为化学诱导脊髓损伤后损伤预测标志物的作用。因此,通过椎管内注射 KA 诱导 Balb/c 成年小鼠体内兴奋性中毒,而体外脊髓兴奋性中毒则是通过沐浴施加 KA 产生的。应用 KA 会诱发神经元大量缺失、后肢运动协调性恶化和热异感。此外,免疫组化分析表明,应用 KA 会导致腹侧角和背侧三至四层的 CREB 阳性核数目减少。我们的数据表明,兴奋毒性诱导的神经元损失可能是由 CREB 核转位的改变所预测的。
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.