title: A substance P mediated pathway contributes to 6-hydroxydopamine induced cell death.
abstract: The neurotoxin 6-hydroxydopamine (6-OHDA) is used to induce dopaminergic cell death, resulting in insufficient striatal dopamine content in the basal ganglia and motor dysfunction typical of Parkinson's disease. Dopamine induces release of the neuropeptide substance P (SP) within the substantia nigra, whereas SP is able to potentiate striatal dopamine release, thus creating a positive feedback mechanism. Previous studies, however, have shown that elevated SP is detrimental to neuronal survival and motor function in acute brain injury. In the current study, we demonstrate that 6-OHDA increases SP production in meso-striatal organotypic co-culture. Moreover, there was a significant correlation between SP content and lactate dehydrogenase release, a marker of cell death, suggesting elevated SP production may contribute to 6-OHDA induced cell death in vitro.
authors.affiliation: Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Emma.Thornton@adelaide.edu.au
authors.forename: Emma
authors.initials: E
authors.lastname: Thornton
authors.forename: Tuyet T B
authors.initials: TT
authors.lastname: Tran
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014574:Uronic Acids / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D018377:Neurotransmitter Agents; D014574:Uronic Acids; D013373:Substance P; D016627:Oxidopamine; C041665:N-acetyltalosaminuronic acid; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase