title: Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress.
abstract: Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously we demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown. This study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity. Furthermore, the portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated CaMKII, pCaMKII), and the glutamate receptor sub-type (NMDA(2B)) expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or imipramine treatment. Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and glutamate receptor levels.
authors.affiliation: J Crayton Pruitt Family Department of Biomedical Engineering and Evelyn F & William L Mcknight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Lin
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Gaowen
authors.initials: G
authors.lastname: Li
authors.forename: Subramaniam G
authors.initials: SG
authors.lastname: Shyamala
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barish
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Vernon
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.forename: William O
authors.initials: WO
authors.lastname: Ogle
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000929:Antidepressive Agents, Tricyclic; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003474:Curcumin; D007099:Imipramine; D003345:Corticosterone