Subchronic Early Life Arsenic Exposure at Low Doses Impaired the Biogenic Amine Neurotransmitter and Nitric Oxide Levels in Different Brain Regions of Rats

摘要

Current approaches to risk assessment assume the neurotoxic response for arsenic at the low doses while the mechanism of arsenic-induced developmental neurotoxicity is unknown. Because of this, our previous studies point out that arsenic-induced cholinergic and dopaminergic dysfunctions with associated behavior and also observed the persistent effects were more pronounced in dopaminergic system in early life exposed rats. In continuation of previous studies, rats were exposed to arsenic in drinking water at low doses (2 or 4 mg/kg) during early life. Here, we investigated that alteration in the levels of biogenic amines and their metabolites (norepinephrine (NE), epinephrine (EPN), dopamine (DA), 3, 4-Dihydroxyphenylacetic acid (DOPAC), Homovanillic acid (HVA) and 5-hydroxytryptamine (5-HT) by using reversed phase high performance liquid chromatography in different brain regions of arsenic exposed rats on PD60 as compared to controls and furthermore determine persistent effect of arsenic after withdrawal of exposure. Levels of nitric oxide (NO) were also declines in brain regions of arsenic-treated rats in different brain regions of early life exposed rats. Arsenic has been found to modulate the monoaminergic and nitrergic systems during the critical periods of brain development; however, these modifications get more compromised in corpus striatum than frontal cortex and hippocampus even after withdrawal of exposure on PD90 as compared to controls. Modification at the level of biogenic amines and NO in certain brain regions would provide opportunities for the development of therapeutics tools for minimizing developmental neurotoxicity.