title: Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human neural progenitor cells: a combined study of metabolomics and morphological analysis.
abstract: Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100 nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases.
authors.affiliation: Health Risk Research Section, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8606, Japan.
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.forename: Hiromi
authors.initials: H
authors.lastname: Akanuma
authors.forename: Feifei
authors.initials: F
authors.lastname: Wei
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagano
authors.forename: Qin
authors.initials: Q
authors.lastname: Zeng
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imanishi
authors.forename: Seiichiroh
authors.initials: S
authors.lastname: Ohsako
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshinaga
authors.forename: Junzo
authors.initials: J
authors.lastname: Yonemoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanokura
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D053801:Capillary Electrochromatography; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D025341:Principal Component Analysis; D053719:Tandem Mass Spectrometry; D013792:Thalidomide / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007166:Immunosuppressive Agents; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D013792:Thalidomide; D014446:Tyrosine 3-Monooxygenase; D005978:Glutathione