Central nervous system targets of chronic arsenic exposure Chapter uri icon

abstract

  • The worldwide presence of arsenic and its impact on human health, affecting millions of exposed individuals through polluted drinking water and soils, has motivated intensive research during the last two decades. The central nervous system is one of the main arsenic targets, and although it has been well documented since the last century that arsenic poisoning causes serious damage ranging from peripheral neuropathy to death, low chronic exposure is today the most relevant concern. Neurotoxic effects include cognitive dysfunction, alterations in verbal comprehension, decrease in attention and long-term memory in children and adolescents. In adults, alterations in learning, concentration and recent memory formation have been reported. With the help of animal models, the underlying basis of these alterations have been investigated from morphological, neurochemical and behavioral perspectives. This chapter focuses on disturbances associated with the process of arsenic methylation that have been observed in essential nervous system constituents such as myelin and neurotransmitters, and the connection with hepatic transformation of arsenic in its methylated species for excretion. The experiments referred to here demonstrate that chronic exposure to low arsenic levels decrease performance in behavioral tasks and modify the methylation of DNA regions encoding for proteins related with neuronal plasticity, leading potentially to epigenetic long lasting changes. Behavioral effects of arsenic are observed in the absence of any toxic manifestation and could be related to interferences with signaling pathways, enzyme and DNA changes which may trigger degenerative processes later in life. Indeed, cytoskeletal modifications, altered processing of amyloid precursor protein (APP) and demyelination are hallmarks of low level arsenic exposure. In light of current hypothesis of arsenic neurotoxic mechanisms, the recent discoveries are gathered in this review to provide links between investigation lines on arsenic toxicity and future research directions. © 2013 by Nova Science Publishers, Inc. All rights reserved.

publication date

  • 2013-01-01