Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase and cognitive enhancing potentials with limited information on their scientific basis and how they regulate gene expression.This study sought to evaluate the in vitro effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity, their mRNA gene expression level and adenosine deaminase (ADA) in cadmium (Cd)‐treated rats. Animals were divided into six groups (n=6): group 1 [(control) received saline/vehicle], group 2 [saline plus curcumin (25 mg/kg)], group 3 [saline plus curcumin (50 mg/kg)], group 4 [Cd (2.5 mg/kg) plus vehicle], group 5 [Cd (2.5 mg/kg) plus curcumin (25 mg/kg)] and group 6 [Cd (2.5 mg/kg) plus curcumin (50 mg/kg)] by oral gavage for 7 days. Acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities were determined and AChE expression was analyzed out using real time polymerase chain reaction (RT‐qPCR).The results of this study revealed that ADA activity was increased in Cd‐poisoned rats, and curcumin co‐treatment reversed this effect comparable to the control. Also, it was observed that acute administration of Cd increased AChE activity and caused a significant (P<0.05) increase in AChE mRNA levels in whole cerebral cortex when compared to control group. However, co‐treatment with curcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd‐treated rats. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfhydryl (−SH) group and nitric oxide (NO). However, the co‐treatment with curcumin at 25 and 50 mg/kg, respectively increased the non‐enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level.In conclusion, inhibition of AChE and ADA activities, suppression of AChE mRNA gene expression level in Cd exposed rats, as well as increased antioxidant status by curcumin in Cd‐induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric‐derived compound in treating neurological disorders including Alzheimer's disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.