Xu Y, Li S, Vernon MM, Pan J, Chen L, Barish PA, Zhang Y, Acharya AP, Yu J, Govindarajan SS, Boykin E, Pan X, O'Donnell JM, Ogle WO. (2011) J Neurochem. 2011 Jun 20. [Epub ahead of print]
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.
Pretreatment 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 (PKA) activity and phosphorylation of cAMP response element-binding protein (pCREB) 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.