title: Targeting 5-HT(1A) receptors in astrocytes to protect dopaminergic neurons in Parkinsonian models.
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.
authors: Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Ikuko
authors: I
authors: Miyazaki
authors: Masato
authors: M
authors: Asanuma
authors: Shinki
authors: S
authors: Murakami
authors: Mika
authors: M
authors: Takeshima
authors: Nao
authors: N
authors: Torigoe
authors: Yoshihisa
authors: Y
authors: Kitamura
authors: Ko
authors: K
authors: Miyoshi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D002065:Buspirone / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D014867:Water / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D017366:Serotonin Receptor Agonists; D014867:Water; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D002065:Buspirone
keywords: 5-HT(1A) receptor; 8-OH-DPAT; Astrocyte; Metallothionein; Neuroprotection; Parkinson's disease