Effects of 6-Hydroxydopamine Exposure on Motor Activity and Biochemical Expression in Zebrafish (Danio Rerio) Larvae

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, current treatments for PD are mainly palliative. Recently, researchers discovered that neurotoxins can induce Parkinsonian-like symptoms in zebrafish. No study to date has investigated the characteristics of PD, such as neuroinflammation factors, oxidative stress, or ubiquitin dysfunction, in this model. Therefore, the current study was aimed at utilizing commonly used clinical drugs, minocycline, vitamin E, and Sinemet, to test the usefulness of this model. Previous studies had indicated that DA cell loss was greater with 6-hydroxydopamine (6-OHDA) than with other neurotoxins. Thus, we first challenged zebrafish with 6-OHDA immersion and found a significant reduction in zebrafish locomotor activity; we then reversed the locomotor disruptions by treatment with vitamin E, Sinemet, or minocycline. The present study also analyzed the mRNA expression of parkin, pink1, and cd-11b, because the expression of these molecular targets has been shown to result in attenuation in mammalian models of PD. Vitamin E, Sinemet, and minocycline significantly reversed 6-OHDA-induced changes of parkin, pink1, and cd-11b mRNA expression in zebrafish. Moreover, we assessed tyrosine hydroxylase (TH) expression to confirm the therapeutic effects of vitamin E tested on this PD model and established that vitamin E reversed the 6-OHDA-induced damage on TH expression. Our results provide some support for the validity of this in vivo Parkinson's model, and we hope that this model will be more widely used in the future.

The 1-Tosylpentan-3-one Protects against 6-Hydroxydopamine-Induced Neurotoxicity

“…Similarly, this study used 6-OHDA to induce damage in dopaminergic neurons in zebrafish larvae and used a software to record and analyze the typical path and swimming distance of zebrafish larvae in real-time. Our team also used this zebrafish imaging system to evaluate several clinical drugs such as a-tocopherol, minocycline, Sinemet, and others, and confirmed the relationship between this model and inflammation, oxidative stress, and death of dopaminergic neurons, through analysis of molecular markers such as TH, THF-α, pink1, and parkin [72]. This study also verified the feasibility and practicality of the zebrafish model.…”

The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling

“…SNS activity is mediated by catecholamines, such as NA, and synthesized by the rate-limiting enzyme Tyrosine hydroxylase (Th1) and converted from dopamine by Dopamine β hydroxlase (Dbh). To determine if the effect of neuronal serotonin on HSPCs was mediated locally by the SNS, embryos were treated with the neurotoxic compound 6-hydroxydopamine (6-OHDA, 200μM) and DBH inhibitor (nepicastat, 30μM) to induce lesions in catecholaminergic neurons and prohibit NA synthesis, respectively (Feng et al, 2014; Stewart et al, 2004). SNS loss was confirmed by WISH for th1 at the sympathetic ganglion ( Figure 4A ).…”

Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

“…We established an in vivo zebrafish PD model in our previous study [21]. In the present study, we examined the therapeutic effects of 11-de in zebrafish.…”

“…Embryos were collected after natural spawning, staged according to standard criteria, and raised synchronously at 28.5 °C in Hank’s buffer. The locomotor behavior test of zebrafish larvae was performed as per the details in a previous study [21]. …”