Effects of 6-hydroxydopamine exposure on motor activity and biochemical expression in zebrafish (Danio rerio) larvae.
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.
1 Department of Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica , Kaohsiung, Taiwan .
Chien-Wei
CW
Feng
Zhi-Hong
ZH
Wen
Shi-Ying
SY
Huang
Han-Chun
HC
Hung
Chun-Hong
CH
Chen
San-Nan
SN
Yang
Nan-Fu
NF
Chen
Hui-Min
HM
Wang
Chung-Der
CD
Hsiao
Wu-Fu
WF
Chen
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004338:Drug Combinations; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D013565:Sympatholytics / Q000494:pharmacology*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D000978:Antiparkinson Agents; D015415:Biomarkers; D004338:Drug Combinations; D013565:Sympatholytics; D029961:Zebrafish Proteins; C009265:carbidopa, levodopa drug combination; D014810:Vitamin E; D007980:Levodopa; D016627:Oxidopamine; D008911:Minocycline; D002230:Carbidopa