title: Curcumin prevents corticosterone-induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway.
abstract: Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT(1A), 5-HT(2A) and 5-HT(4), but 5-HT(1B,) 5-HT(2B), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT(1A) and 5-HT(4) receptors, but not for the 5-HT(2A) receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT(1A) receptor antagonist p-MPPI or 5-HT(4) receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, USA. yingxufl@yahoo.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Vernon
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barish
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Abhinav P
authors.initials: AP
authors.lastname: Acharya
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Subramaniam S
authors.initials: SS
authors.lastname: Govindarajan
authors.forename: Erin
authors.initials: E
authors.lastname: Boykin
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.forename: James M
authors.initials: JM
authors.lastname: O'Donnell
authors.forename: William O
authors.initials: WO
authors.lastname: Ogle
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D050882:CREB-Binding Protein / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003345:Corticosterone / Q000633:toxicity*; D003474:Curcumin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000235:genetics / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D050882:CREB-Binding Protein; D003345:Corticosterone; D003474:Curcumin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005473:Fluoxetine; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors