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Astrocytic expression of GSTA4 is associated to dopaminergic neuroprotection in a rat 6-OHDA model of Parkinson’s disease

Jewett, Michael LU ; Jimenez, Itzia LU and Swanberg, Maria LU (2017) In Brain Sciences 7(7).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
6-OHDA, Dopaminergic neurons, GSTA4, Neuroprotection, Parkinson’s disease, Vra1
in
Brain Sciences
volume
7
issue
7
external identifiers
  • scopus:85021758598
  • wos:000407444400004
DOI
10.3390/brainsci7070073
language
English
LU publication?
yes
id
5f2ef022-1c98-4b96-9dda-7f962c9c8f09
date added to LUP
2017-07-18 14:46:56
date last changed
2017-09-18 11:38:34
@article{5f2ef022-1c98-4b96-9dda-7f962c9c8f09,
  abstract     = {<p>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 &lt; 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 &lt; 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.</p>},
  articleno    = {73},
  author       = {Jewett, Michael and Jimenez, Itzia and Swanberg, Maria},
  keyword      = {6-OHDA,Dopaminergic neurons,GSTA4,Neuroprotection,Parkinson’s disease,Vra1},
  language     = {eng},
  month        = {07},
  number       = {7},
  series       = {Brain Sciences},
  title        = {Astrocytic expression of GSTA4 is associated to dopaminergic neuroprotection in a rat 6-OHDA model of Parkinson’s disease},
  url          = {http://dx.doi.org/10.3390/brainsci7070073},
  volume       = {7},
  year         = {2017},
}