Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson’s disease mouse model

Abstract

BackgroundGastrodia elata Blume (GEB), commonly used medicinal herb, has been reported as a promising candidate for neurodegenerative diseases such as Parkinson’s disease. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the gold-standard drug for Parkinson’s disease, but long-term treatment results in the L-dopa-induced dyskinesia (LID). This study was undertaken to examine the beneficial effects of GEB on L-DOPA induced dyskinesia in 6-hydroxydopamine (6-OHDA)-induced experimental Parkinsonism.MethodsWe tested the effects of GEB on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. To analyze the dyskinetic anomalies, we measured abnormal involuntary movement (AIM). Immunohistological analyses of pERK and FosB expressions in the striatum are performed to explore the mechanism of GEB on LID.ResultsThe finding of this study demonstrated that GEB (200, 400 and 800 mg/kg) alleviated L-dopa induced AIMs in a dose-dependent manner. In each integrative AIM subtype analysis, we also found that the GEB (400 and 800 mg/kg) treatment decreased L-DOPA-induced axial, limb, orolingual, and locomotive AIMs compared to the LID group. In addition, GEB normalized the abnormal LID-induced increase of pERK1/2 and FosB, the immediate early genes of LID in the striatum.ConclusionsIn conclusion, our results provide a novel insight into the pharmacological actions of GEB that could have a benefit for PD patients through the reduction of LID.

Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

“…In normal animals, p-ERK1/2 and FosB/ΔFosB can be both induced by physiological stimuli (Kuroda et al, 2007; Perrotti et al, 2013). Similarly, p-ERK1/2 and FosB/ΔFosB were also upregulated in a model of Parkinson’s disease (Doo et al, 2014). Indeed, lines of evidence support the possibility that p-ERK1/2 can directly regulate FosB levels (Kuroda et al, 2007).…”

The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures

“…In this study, gastrodin, used as a treatment for epileptiform discharges induced by Mg 2+ -free medium, which is regarded as NMDA receptor-mediated spontaneous activity, showed no efficacy. Low magnesium medium induces epileptiform activity in hippocampal slices, and is commonly used for screening chemicals with anti-convulsive effects (10). Glutamate and NMDA receptors are the key factors for low extracellular magnesium-induced epileptiform activity in hippocampal slices (22,23).…”

Electroacupuncture alleviates Parkinson disease and regulates the expression of brain-gut peptides

“…AIM score of each rat was evaluated at 2, 7, and 14 days after the first 6-OHDA injection. As previously reported [ 11 ], AIM tests were classified into four subtypes: axial AIM, defined as upper body and neck contralateral twisted posturing; limb AIM, defined as repeated, rhythmic jerking or dystonic posturing of the forelimb on the side contralateral to the lesion; Orolingual AIM, characterized by empty jaw movements and contralateral tongue protrusion; and locomotion AIM, indicated by the increased locomotion with contralateral side bias. The total AIM score was calculated by combining each of the individual dyskinesia scores.…”