www.elsevier.com/locate/brainres Available online at www.sciencedirect.com Research Report Methionine-enriched diet decreases hippocampal antioxidant defences and impairs spontaneous behaviour and long-term potentiation in rats Alessandro Viggiano a,n , Emanuela Viggiano a , Marcellino Monda a , Diego Ingrosso b , Alessandra F. Perna c , Bruno De Luca a a Department of Experimental Medicine—Section of Human Physiology, Second University of Naples, via De Crecchio 8, 80138 Naples, Italy b Department of Biochemistry and Biophysics ‘‘F. Cedrangolo’’, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy c First Division of Nephrology, Department of Clinical and Experimental Internal Medicine, Second University of Naples, via Pansini 5, 80131 Naples, Italy article info Article history: Accepted 28 June 2012 Available online 8 July 2012 Keywords: Hyperhomocysteinemia Methionine Neurodegenerative diseases Memory Anxiety Long-term potentiation Superoxide dismutase abstract Diets high in methionine lead to elevation of plasma homocysteine levels which are possibly linked to neurodegenerative diseases and oxidative stress. In the present study, we investigated the effects of methionine-enriched diet on antioxidant defences, on rat spontaneous behaviour and on the ability to sustain long-term potentiation in the dentate gyrus (DG). Sprague-Dawley rats were fed either a standard laboratory diet or a methionine enriched-diet (1% or 5% methionine in drinking water) for 8 weeks. After the 8 weeks, the animals were tested for spontaneous motor activity and habituation in an open field maze, for anxiety-like behaviour in an elevated plus maze and for the ability to sustain long-term potentiation (LTP) induced in the dentate gyrus under urethane anaesthesia. The brains were then removed and histochemically stained for superoxide dismutase (SOD) activity. Rats fed on 5% methionine significantly reduced total distance travelled during the open field test and exhibited no habituation with respect to the other two groups. Rats fed on 5% methionine also showed a significant increase of the anxiety level. Moreover, in this group, the ability to induce LTP in DG was impaired. SOD activity was significantly increased in the cerebral cortex of the rats fed on 1% and 5% methionine with respect to the control group. In conclusion, 5% methionine in drinking water led to evident impairment of locomotor skills and of synaptic plasticity. SOD activity in the cortex was increased in both the groups fed on 1% and 5% methionine, thus suggesting that metabolic adjustments, triggered by the methionine-enriched diet, are likely mediated by reactive oxygen species. & 2012 Elsevier B.V. All rights reserved. 0006-8993/$ - see front matter & 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.brainres.2012.06.048 n Corresponding author. Fax: þ39 081 566 5823. E-mail address: alessandro.viggiano@unina2.it (A. Viggiano). brain research 1471 (2012) 66–74