Next Article in Journal / Special Issue
Hypermethylation of Synphilin-1, Alpha-Synuclein-Interacting Protein (SNCAIP) Gene in the Cerebral Cortex of Patients with Sporadic Parkinson’s Disease
Previous Article in Journal / Special Issue
Clinicopathological Phenotype and Genetics of X-Linked Dystonia–Parkinsonism (XDP; DYT3; Lubag)
Article Menu

Export Article

Open AccessArticle
Brain Sci. 2017, 7(7), 73; doi:10.3390/brainsci7070073

Astrocytic Expression of GSTA4 Is Associated to Dopaminergic Neuroprotection in a Rat 6-OHDA Model of Parkinson’s Disease

Translational Neurogenetics Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, Sölvegatan 17, 221 84 Lund, Sweden
*
Author to whom correspondence should be addressed.
Academic Editors: Steven Frucht and Pichet Termsarasab
Received: 29 May 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
View Full-Text   |   Download PDF [3579 KB, uploaded 26 June 2017]   |  

Abstract

Idiopathic Parkinson’s disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD. We therefore investigated whether PVG alleles in Vra1 are neuroprotective in a toxin-induced model of PD and if this effect is coupled to Gsta4. We performed unilateral 6-hydroxydopamine (6-OHDA) partial lesions in the striatum and compared the extent of neurodegeration in parental (DA) and congenic (DA.VRA1) rats. At 8 weeks after 6-OHDA lesion, DA.VRA1 rats displayed a higher density of remaining dopaminergic fibers in the dorsolateral striatum compared to DA rats (44% vs. 23%, p < 0.01), indicating that Vra1 alleles derived from the PVG strain protect dopaminergic neurons from 6-OHDA toxicity. Gsta4 gene expression levels in the striatum and midbrain were higher in DA.VRA1 congenic rats compared to DA at 2 days post-lesion (p < 0.05). The GSTA4 protein co-localized with astrocytic marker GFAP, but not with neuronal marker NeuN or microglial marker IBA1, suggesting astrocyte-specific expression. This is the first report on Vra1 protective effects on dopaminergic neurodegeneration and encourages further studies on Gsta4 in relation to PD susceptibility. View Full-Text
Keywords: Parkinson’s disease; Vra1; 6-OHDA; neuroprotection; dopaminergic neurons; GSTA4 Parkinson’s disease; Vra1; 6-OHDA; neuroprotection; dopaminergic neurons; GSTA4
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Jewett, M.; Jimenez-Ferrer, I.; Swanberg, M. Astrocytic Expression of GSTA4 Is Associated to Dopaminergic Neuroprotection in a Rat 6-OHDA Model of Parkinson’s Disease. Brain Sci. 2017, 7, 73.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Brain Sci. EISSN 2076-3425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top