title: Regeneration of dopaminergic neurons after 6-hydroxydopamine-induced lesion in planarian brain.
abstract: Planarians have robust regenerative ability dependent on X-ray-sensitive pluripotent stem cells, called neoblasts. Here, we report that planarians can regenerate dopaminergic neurons after selective degeneration of these neurons caused by treatment with a dopaminergic neurotoxin (6-hydroxydopamine; 6-OHDA). This suggests that planarians have a system to sense the degeneration of dopaminergic neurons and to recruit stem cells to produce dopaminergic neurons to recover brain morphology and function. We confirmed that X-ray-irradiated planarians do not regenerate brain dopaminergic neurons after 6-OHDA-induced lesioning, suggesting that newly generated dopaminergic neurons are indeed derived from pluripotent stem cells. However, we found that the majority of regenerated dopaminergic neurons were 5-bromo-2'-deoxyuridine-negative cells. Therefore, we carefully analyzed when proliferating stem cells became committed to become dopaminergic neurons during regeneration by a combination of 5-bromo-2'-deoxyuridine pulse-chase experiments, immunostaining/in situ hybridization, and 5-fluorouracil treatment. The results strongly suggested that G(2) -phase stem cells become committed to dopaminergic neurons in the mesenchymal space around the brain, after migration from the trunk region following S-phase. These new findings obtained from planarian regeneration provide hints about how to conduct cell-transplantation therapy for future regenerative medicine.
authors: Department of Biophysics, Graduate School of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto, Japan.
authors: Kaneyasu
authors: K
authors: Nishimura
authors: Takeshi
authors: T
authors: Inoue
authors: Kanji
authors: K
authors: Yoshimoto
authors: Takashi
authors: T
authors: Taniguchi
authors: Yoshihisa
authors: Y
authors: Kitamura
authors: Kiyokazu
authors: K
authors: Agata
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D010932:Planarians; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000528:radiation effects; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D009498:Neurotoxins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D001973:Bromodeoxyuridine; D005472:Fluorouracil; D004298:Dopamine