Reversibility of changes in brain cholinergic receptors and acetylcholinesterase activity in rats following early life arsenic exposure |
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| Affiliation: | 1. CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, 226 001, India;2. Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, 110 062, India;3. Department of Criminology and Forensic Science, Harisingh Gour University, Sagar,- 470003, India;1. Department of Normal Physiology, Yaroslavl State Medical Academy, Revoliucionnaya 5, Yaroslavl 150000, Russia;2. Department of Physiology, St. Petersburg State University, St. Petersburg, Russia;3. Kazan (Volga Region) Federal University, Kazan, Russia;4. Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium;1. Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan;2. Department of Obstetrics and Gynecology, Shikoku Medical Center for Children and Adults, Senyu-cho 2-1-1, Zentsuji City, Kagawa 765-8507, Japan;3. Department of Reproductive Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan;1. Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia;2. Department of Biochemistry and Goodman Cancer Research Centre, McGill University, 1160 Pine Ave. West, H3A 1A3 Montreal, QC, Canada;1. Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, Milan, Italy;2. Scientific Department, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, Milan, Italy;3. Department of (Neuro)Pathology, Academic Medical Center, The Netherlands;4. Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, The Netherlands;5. SEIN – Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands;1. Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;2. Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;3. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil |
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| Abstract: | In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC β-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects. |
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| Keywords: | Arsenic Learning and memory Cholinergic receptors Oxidative stress Apoptosis |
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