e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 7 ( 2 0 1 4 ) 916–927 Available online at www.sciencedirect.com ScienceDirect j o ur nal ho me pa ge: www.elsevier.com/locate/etap Acetylsalicylic acid and ascorbic acid combination improves cognition; Via antioxidant effect or increased expression of NMDARs and nAChRs? Yusuf Kara a , Duygu Kumbul Doguc b,∗ , Esin Kulac c , Fatih Gultekin b a Serik Central Hospital, Medical Biochemistry Department, Antalya, Turkey b Suleyman Demirel University, Medical Faculty, Medical Biochemistry Department, Isparta, Turkey c Kocaeli University, Medical Faculty, Education of Medicine Department, Kocaeli, Turkey a r t i c l e i n f o Article history: Received 3 June 2013 Received in revised form 20 February 2014 Accepted 24 February 2014 Available online 3 March 2014 Keywords: Acetylsalicylic acid Spatial memory Ageing NMDARs nAChRs a b s t r a c t Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expres- sions of NR2A, NR2B, nAChR7, 4 and 2. Forty male rats (16–18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin + ascorbic acid- treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin + ascorbic acid group (p < 0.05). While 8- hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChR7 expressions were significantly increased in the aspirin + ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin + ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Ageing is characterized by a progressive functional decline and finally diverse effects on cognition and underlying neural systems (Gould and Feiro, 2005; Jung et al., 2006). ∗ Corresponding author. Tel.: +90 2462119416; fax: +90 2462370240. E-mail addresses: hykara@hotmail.com (Y. Kara), duygukd@yahoo.com, doguc@sdu.edu.tr (D.K. Doguc), kulacesin@yahoo.com (E. Kulac), drfatih2000@hotmail.com (F. Gultekin). Regression in learning and memory performance as a result of age-mediated structural and functional changes in the hip- pocampus has been well established (Farooqui and Farooqui, 2009; Rosenzweig and Barnes, 2003). During ageing, enhancement of production of COX-derived reactive species as well as increase in proinflammatory http://dx.doi.org/10.1016/j.etap.2014.02.019 1382-6689/© 2014 Elsevier B.V. All rights reserved.