{"title":"6-Hydroxydopamine-induced decrease in dopaminergic neurons is avoided by effusol and dehydroeffusol, unique phenanthrenes of Juncus effusus","authors":"","doi":"10.1016/j.phanu.2024.100403","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Excess influx of extracellular Zn<sup>2+</sup> into nigral dopaminergic neurons play a crucial role for 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. On the basis of neurodegeneration by Zn<sup>2+</sup> dysregulation, we aimed to clarify the effect of effusol and dehydroeffusol, unique phenanthrenes from <em>Juncus effusus</em> on dopaminergic degeneration.</p></div><div><h3>Methods</h3><p>The decrease in dopaminergic neurons was assessed by tyrosine hydroxylase immunostaining 14 days after 6-OHDA injection into the substantia nigra pars compacta (SNpc) of rats.</p></div><div><h3>Results</h3><p>The decrease in dopaminergic neurons induced by 6-OHDA was avoided by co-injection of 1<em>-</em>naphthyl acetyl spermine (NASPM), a selective blocker of Zn<sup>2+</sup>-permeable GluR2-lacking AMPA receptors, which blocked the increase in intracellular Zn<sup>2+</sup>, supporting the involvement of Zn<sup>2+</sup> dysregulation in dopaminergic degeneration. Moreover, either effusol or dehydroeffusol was co-injected with 6-OHDA into the SNpc. The decrease in dopaminergic neurons was avoided by effusol and dehydroeffusol. The increases in intracellular Zn<sup>2+</sup> and H<sub>2</sub>O<sub>2</sub> in the SNpc induced by 6-OHDA were also avoided by effusol and dehydroeffusol.</p></div><div><h3>Conclusions</h3><p>The present study first indicates that effusol and dehydroeffusol avoid the decrease in dopaminergic neurons in the SNpc via reducing production of reactive oxygen species induced by intracellular Zn<sup>2+</sup> dysregulation after injection of 6-OHDA into the rat SNpc. It is likely that effusol and dehydroeffusol serve as nutraceutical components to protect dopaminergic degeneration, perhaps via regulating presynaptic excitation of glutamatergic neurons in the SNpc.</p></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PharmaNutrition","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S221343442400029X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Excess influx of extracellular Zn2+ into nigral dopaminergic neurons play a crucial role for 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. On the basis of neurodegeneration by Zn2+ dysregulation, we aimed to clarify the effect of effusol and dehydroeffusol, unique phenanthrenes from Juncus effusus on dopaminergic degeneration.
Methods
The decrease in dopaminergic neurons was assessed by tyrosine hydroxylase immunostaining 14 days after 6-OHDA injection into the substantia nigra pars compacta (SNpc) of rats.
Results
The decrease in dopaminergic neurons induced by 6-OHDA was avoided by co-injection of 1-naphthyl acetyl spermine (NASPM), a selective blocker of Zn2+-permeable GluR2-lacking AMPA receptors, which blocked the increase in intracellular Zn2+, supporting the involvement of Zn2+ dysregulation in dopaminergic degeneration. Moreover, either effusol or dehydroeffusol was co-injected with 6-OHDA into the SNpc. The decrease in dopaminergic neurons was avoided by effusol and dehydroeffusol. The increases in intracellular Zn2+ and H2O2 in the SNpc induced by 6-OHDA were also avoided by effusol and dehydroeffusol.
Conclusions
The present study first indicates that effusol and dehydroeffusol avoid the decrease in dopaminergic neurons in the SNpc via reducing production of reactive oxygen species induced by intracellular Zn2+ dysregulation after injection of 6-OHDA into the rat SNpc. It is likely that effusol and dehydroeffusol serve as nutraceutical components to protect dopaminergic degeneration, perhaps via regulating presynaptic excitation of glutamatergic neurons in the SNpc.