title: Early life arsenic exposure and brain dopaminergic alterations in rats.
abstract: Recently, we found that early life exposure to arsenic at low doses resulted to cause brain cholinergic deficits and exhibited a trend of recovery on withdrawal of arsenic exposure. In continuation to this, the present study has been carried out to assess the impact of low level arsenic exposure on brain dopaminergic system and associated behavior in developing rats and investigate if neurobehavioral changes are recovered or persistent. Early life exposure (PD22-PD59) to arsenic (2 or 4 mg/kg body weight, p.o.) in rats resulted to increase the motor activity on PD60, compared to controls. The hyperactivity in arsenic exposed rats was found to be linked with increase in the binding of DA-D2 receptors (38%, 56%), mRNA expression of DAR-D2 receptor gene (68%, 97%) and expression of tyrosine hydroxylase protein (1.93, 2.73-fold) in the corpus striatum as compared to controls on PD60. Exposure to arsenic enhanced generation of ROS (47%, 84%) and was associated with decrease in the mitochondrial membrane potential (13.3%, 15.33%), activity of mitochondrial complexes and increased oxidative stress. Disruption in the expression of pro-apoptotic, anti-apoptotic and stress marker proteins was also distinct in the corpus striatum of arsenic exposed rats. The severity of changes in the behavioral and neurochemical endpoints were found to persist in rats exposed to arsenic at high dose and exhibited a trend of recovery at low dose on withdrawal of arsenic exposure on PD90. Early life arsenic exposure appears to be critical and vulnerable as development of dopamine receptors continues during this period.
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors.forename: Lalit P
authors.initials: LP
authors.lastname: Chandravanshi
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Shukla
authors.affiliation: Department of Medical Elementology and Toxicology Jamia Hamdard, New Delhi 110 062, India.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors.forename: Aditya B
authors.initials: AB
authors.lastname: Pant
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India. Electronic address: vkkhanna1@gmail.com.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Khanna
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001151:Arsenic / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011954:Receptors, Dopamine; D051028:bcl-2-Associated X Protein; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; D001151:Arsenic; D004298:Dopamine
keywords: Apoptosis; Brain; Dopaminergic system; Mitochondrial dysfunctions; Oxidative stress