Naringenin ameliorates Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular- streptozotocin in rat model

Abstract

Oxidative stress is involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) as well as age related cognitive deficit. The present study was designed to investigate the pre-treatment effects of naringenin (NAR), a polyphenolic compound on cognitive dysfunction, oxidative stress in the hippocampus, and hippocampal neuron injury in a rat model of AD-TNDCI. The rats were pre-treated with NAR at a selective dose (50 mg/kg, orally) for 2 weeks followed by intracerebroventricular- streptozotocin (ICV-STZ) (3 mg/kg; 5 μl per site) injection bilaterally. Behavioral alterations were monitored after 2 weeks from the lesion using passive avoidance test and Morris water maze paradigm. Three weeks after the lesion, the rats were sacrificed for measuring non-enzymatic [4-hydroxynonenal (4-HNE), malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H2O2), protein carbonyl (PC), reduced glutathione (GSH)] content and enzymatic [glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and Na+/K+-ATPase] activity in the hippocampus, and expression of choline acetyltransferase (ChAT) positive neuron, and histopathology of hippocampal neurons. The non-enzymatic level and enzymatic activity was significantly increased and decreased, respectively, with striking impairments in spatial learning and memory, loss of ChAT positive neuron and severe damage to hippocampal neurons in the rat induced by ICV-STZ. These abnormalities were significantly improved by NAR pre-treatment. The study suggests that NAR can protect against cognitive deficits, neuronal injury and oxidative stress induced by ICV-STZ, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD-TNDCI. © 2012 Elsevier Ltd. All rights reserved.