Biochemical Histological and Memory Impairment E

Authors: Amit Pal Rama Kumari Badyal Rakesh Kumar Vasishta Savita Verma Attri Babu Ram Thapa Rajendra Prasad

Publish Date: 2013/04/24

Volume: 153, Issue: 1-3, Pages: 257-268

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Abstract

Animal models of copper toxicosis rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content The aim of this study was to investigate the effects of intraperitoneally injected copper lactate 015 mg Cu/100 g body weight daily for 90 days on copper and zinc levels in the liver and hippocampus on biochemical parameters and on neurobehavioral functions by Morris water maze of male Wistar rats Copperadministered animals exhibited significantly decreased serum acetylcholinesterase AChE activity and impaired neuromuscular coordination and spatial memory compared to control rats Copperintoxicated rats showed significant increase in liver and hippocampus copper content 991 and 73  increase respectively 407  reduction in hepatic zinc content and interestingly 771  increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats Massive grade 4 copper depositions and grade 1 copperassociated protein in hepatocytes of copperintoxicated rats were substantiated by rhodanine and orcein stains respectively Copperintoxicated rats demonstrated swelling and increase in the number of astrocytes and copper deposition in the choroid plexus with degenerated neurons showing pyknotic nuclei and dense eosinophilic cytoplasm In conclusion the present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory and neuromuscular coordination swelling of astrocytes decreased serum AChE activity copper deposition in the choroid plexus neuronal degeneration and augmented levels of copper and zinc in the hippocampus of male Wistar ratsThe authors acknowledge the financial support provided by the Indian Council of Medical Research ICMR New Delhi as JRF/SRF to Mr Amit Pal The authors are thankful to Professor KD Gill for the guidance in carrying out the neurobehavioral studies and Dr Jayagandhan J for the suggestions and revision of the manuscript The authors also acknowledge the support of Mr Charan Singh for the staining studies Mr Rakesh Mohindra for the statistics and Mrs Minni for the metal analysis

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