6-Hydroxydopamine-induced decrease in dopaminergic neurons is avoided by effusol and dehydroeffusol, unique phenanthrenes of Juncus effusus

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.