TY - JOUR
T1 - Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice
AU - Rajasekar, N.
AU - Dwivedi, Subhash
AU - Tota, Santosh Kumar
AU - Kamat, Pradeep Kumar
AU - Hanif, Kashif
AU - Nath, Chandishwar
AU - Shukla, Rakesh
N1 - Funding Information:
Financial support to NR and SD from Indian Council of Medical Research, New Delhi and PKT, and SKT from Council of Scientific and Industrial Research, New Delhi is gratefully acknowledged.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Cerebral blood flow
KW - Cholinergic dysfunction
KW - Curcumin
KW - Memory
KW - Neuroinflammation
KW - Okadaic acid
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U2 - 10.1016/j.ejphar.2013.04.033
DO - 10.1016/j.ejphar.2013.04.033
M3 - Article
C2 - 23685326
AN - SCOPUS:84885479169
SN - 0014-2999
VL - 715
SP - 381
EP - 394
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -