Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice

N. Rajasekar, Subhash Dwivedi, Santosh Kumar Tota, Pradeep Kumar Kamat, Kashif Hanif, Chandishwar Nath, Rakesh Shukla

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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 (100 ng, 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 (Ca2+)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 (50 mg/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 (Ca2+)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.

Original languageEnglish (US)
Pages (from-to)381-394
Number of pages14
JournalEuropean Journal of Pharmacology
Volume715
Issue number1-3
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Cerebral blood flow
  • Cholinergic dysfunction
  • Curcumin
  • Memory
  • Neuroinflammation
  • Okadaic acid

ASJC Scopus subject areas

  • Pharmacology

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