Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models

Ikuko Miyazaki, Masato Asanuma, Shinki Murakami, Mika Takeshima, Nao Torigoe, Yoshihisa Kitamura, Ko Miyoshi

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)244-256
Number of pages13
JournalNeurobiology of Disease
Volume59
DOIs
Publication statusPublished - Nov 2013

Keywords

  • 5-HT receptor
  • 8-OH-DPAT
  • Astrocyte
  • Metallothionein
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology

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