Research Report Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer's type Tauheed Ishrat 1 , Kehkashan Parveen, Mohd. Moshahid Khan, Gulrana Khuwaja, M. Badruzzaman Khan, Seema Yousuf, Ajmal Ahmad, Pallavi Shrivastav, Fakhrul Islam ⁎ Department of Medical Elementology and Toxicology, Neurotoxicology Laboratory, Jamia Hamdard (Hamdard University), New Delhi–110062, India ARTICLE INFO ABSTRACT Article history: Accepted 4 April 2009 Available online 15 April 2009 Selenium (Se), a nutritionally essential trace element with known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. Intracerebroventricular-streptozotocin (ICV-STZ) in rats causes impairment of brain glucose and energy metabolism along with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (SDAT). The present study demonstrates the therapeutic efficacy of Se on cognitive deficits and oxidative damage in ICV-STZ in rats. Male Wistar rats were pre-treated with sodium selenite, a salt of Se (0.1 mg/kg; body weight) for 7 days and then were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle. After two ICV- STZ infusions, rats were tested for memory deficits in passive avoidance and Morris water maze (MWM) tests and then were sacrificed for biochemical and histopatholgical assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by Se supplementation. A significant increase in thio-barbituric acid reactive species (TBARS), protein carbonyl (PC) and a significant decrease in reduced glutathione (GSH), antioxidant enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and adenosine triphosphate (ATP) in the hippocampus and cerebral cortex and choline acetyltransferase (ChAT) in hippocampus were observed in ICV-STZ rats. Se supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. Our study reveals that Se, as a powerful antioxidant, prevents cognitive deficits, oxidative damage and morphological changes in the ICV-STZ rats. Thus, it may have a therapeutic value for the treatment of SDAT. © 2009 Published by Elsevier B.V. Keywords: Sodium selenite Cognitive deficits Oxidative damage Choline acetyltransferase Adenosine triphosphate Streptozotocin Sporadic dementia of Alzheimer's type 1. Introduction Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. It is the leading cause of senile dementia and is characterized by memory and cognitive loss, the formation of beta-amyloid peptide plaques, neurofibrillary tangles and BRAIN RESEARCH 1281 (2009) 117 – 127 ⁎ Corresponding author. Fax: +91 11 2605 9663. E-mail addresses: tauheedarshi@gmail.com (T. Ishrat), fislam2001@yahoo.co.in (F. Islam). 1 Present address: Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA 30322, USA. 0006-8993/$ – see front matter © 2009 Published by Elsevier B.V. doi:10.1016/j.brainres.2009.04.010 available at www.sciencedirect.com www.elsevier.com/locate/brainres