Nov, 2013
Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models
Neurobiology of Disease
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- Volume
- 59
- Number
- 59
- First page
- 244
- Last page
- 256
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.nbd.2013.08.003
Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-HT1A) agonist 8-OH-DPAT induced astrocyte proliferation and increased metallothionein-1/-2 (MT-1/-2), antioxidative molecules, in cultured astrocytes and the striatum of mice. Primary cultured mesencephalic dopamine neurons were protected against oxidative stress by preincubation with conditioned media from 8-OH-DPAT-treated astrocytes. These protective effects were canceled by 5-HT1A antagonist or MT-1/-2-specific antibody. Furthermore, reduction of nigrostriatal dopaminergic neurons in 6-hydroxydopamine-lesioned parkinsonian model mice was significantly abrogated by repeated injections of 8-OH-DPAT. Treatment with 8-OH-DPAT markedly increased the expression of MT in striatal astrocytes in the hemi-parkinsonian mice. Our study provides a promising therapeutic strategy of neuroprotection against oxidative stress and progressive dopaminergic neurodegeneration by demonstrating the efficacy of targeting 5-HT1A receptors in astrocytes. © 2013 Elsevier Inc.
- Link information
- ID information
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- DOI : 10.1016/j.nbd.2013.08.003
- ISSN : 0969-9961
- ISSN : 1095-953X
- Pubmed ID : 23959140
- SCOPUS ID : 84883306197