Research Report Influence of age on aluminum induced lipid peroxidation and neurolipofuscin in frontal cortex of rat brain: A behavioral, biochemical and ultrastructural study Sandeep Tripathi a , Abbas Ali Mahdi a, ⁎, Akbar Nawab a , Ramesh Chander a , Mahdi Hasan b , Mohammad Shakil Siddiqui b , Farzana Mahdi c , Kalyan Mitra d , Virendra Kumar Bajpai d a Medical Elementology and Free Radical Biology Laboratory, Department of Biochemistry, King George's Medical University, Lucknow, 226003, India b Department of Anatomy, King George's Medical University, Lucknow, 226003, India c Department of Biochemistry, Era's Lucknow Medical College, Lucknow, 226003, India d Electron Microscopy Division, Central Drug Research Institute, Lucknow, 226003, India ARTICLE INFO ABSTRACT Article history: Accepted 14 November 2008 Available online 3 December 2008 Aluminum exposure is known to be associated with oxidative stress and cognitive decline in experimental animals but the precise mechanism of its neurotoxicity has not yet been delineated. The present study attempts to assess the learning and memory capacity of rats using Y-maze test for cognitive functioning. The markers of oxidative stress, e.g. lipid peroxides and endogenous antioxidants as well as metals (Al, Fe, Cu, Zn and Se) were measured in the brain frontal cortex of young and aged rats fed with AlCl 3 (100 mg/kg b.w.) for 90 days and normal saline treated controls. We observed significant changes between young and aged Al treated rats and their controls in terms of lipid peroxides and endogenous antioxidants. Lipofuscin content was significantly increased in Al treated aged rats along with higher concentration of Al, Fe and Zn with concomitantly low levels of Cu, and Se. Ultrastructural studies of the frontal cortex of exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of spongiform lipofuscin, vacuolization and lysosomal degradation. Changes in synaptic morphology and decreased number of synapses were detected in the frontal cortex of Al treated aged rats. On the basis of the results of the present study, we conclude that Al may be linked with neurolipofuscinogenesis and alteration in neurobehavioral activity and these changes may be responsible for the development of age related disorders, such as Alzheimer’s disease. © 2008 Elsevier B.V. All rights reserved. Keywords: Aging Aluminum Cognition Frontal cortex Lipofuscin BRAIN RESEARCH 1253 (2009) 107 – 116 ⁎ Corresponding author. Fax: +91 522 2253030. E-mail address: mahdiaa@rediffmail.com (A.A. Mahdi). URL: http://www.mefr.com (A.A. Mahdi). Abbreviations: AD, Alzheimer's Disease; Al, Aluminum; CD, conjugated dienes; CAT, Catalase; GSHPx, Glutathione Peroxidase; SOD, Superoxide dismutase; LF, Lipofuscin; TP, Total Proteins; TL, Total Lipid; PC, Protein Carbonyl; LPO, Lipid peroxidation; LOOH, Lipid hydroperoxide; MDA, Malondialdehyde 0006-8993/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2008.11.060 available at www.sciencedirect.com www.elsevier.com/locate/brainres