title: Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.
abstract: Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment.
authors.affiliation: Division of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, CDRI, P. O. Box 173, Lucknow 226001, India.
authors.forename: N
authors.initials: N
authors.lastname: Rajasekar
authors.forename: Subhash
authors.initials: S
authors.lastname: Dwivedi
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Tota
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Kamat
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
authors.forename: Rakesh
authors.initials: R
authors.lastname: Shukla
mesh_terms: D000109:Acetylcholine; D000110:Acetylcholinesterase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy / Q000517:prevention & control; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019319:Okadaic Acid / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019319:Okadaic Acid; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D000110:Acetylcholinesterase; D005978:Glutathione; D003474:Curcumin; D000109:Acetylcholine; D002118:Calcium
keywords: Cerebral blood flow; Cholinergic dysfunction; Curcumin; Memory; Neuroinflammation; Okadaic acid