Region-Specific Neuroprotective Features of Astrocytes against Oxidative Stress Induced by 6-Hydroxydopamine

In previous studies, we found regional differences in the induction of antioxidative molecules in astrocytes against oxidative stress, postulating that region-specific features of astrocytes lead region-specific vulnerability of neurons. We examined region-specific astrocytic features against dopami...

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Published in:International journal of molecular sciences 2019-01, Vol.20 (3), p.598
Main Authors: Asanuma, Masato, Okumura-Torigoe, Nao, Miyazaki, Ikuko, Murakami, Shinki, Kitamura, Yoshihisa, Sendo, Toshiaki
Format: Article
Language:English
Subjects:
6-Hydroxydopamine
Antioxidants
astrocyte
Astrocytes
Brain
Cysteine
Cystine
Dopamine receptors
Enzymes
Gene expression
Glycine
Homeostasis
Mesencephalon
Neostriatum
Neurodegeneration
Neurons
Neuroprotection
Neurotoxicity
Nrf2
Oxidative stress
phase II detoxifying molecules
Proteins
region-specificity
striatum
Toxins
Transportation systems
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Summary:In previous studies, we found regional differences in the induction of antioxidative molecules in astrocytes against oxidative stress, postulating that region-specific features of astrocytes lead region-specific vulnerability of neurons. We examined region-specific astrocytic features against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) as an oxidative stress using co-culture of mesencephalic neurons and mesencephalic or striatal astrocytes in the present study. The 6-OHDA-induced reduction of mesencephalic dopamine neurons was inhibited by co-culturing with astrocytes. The co-culture of midbrain neurons with striatal astrocytes was more resistant to 6-OHDA than that with mesencephalic astrocytes. Furthermore, glia conditioned medium from 6-OHDA-treated striatal astrocytes showed a greater protective effect on the 6-OHDA-induced neurotoxicity and oxidative stress than that from mesencephalic astrocytes. The cDNA microarray analysis showed that the number of altered genes in both mesencephalic and striatal astrocytes was fewer than that changed in either astrocyte. The 6-OHDA treatment, apparently up-regulated expressions of Nrf2 and some anti-oxidative or Nrf2-regulating phase II, III detoxifying molecules related to glutathione synthesis and export in the striatal astrocytes but not mesencephalic astrocytes. There is a profound regional difference of gene expression in astrocytes induced by 6-OHDA. These results suggest that protective features of astrocytes against oxidative stress are more prominent in striatal astrocytes, possibly by secreting humoral factors in striatal astrocytes.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20030598