Title

Redox Mechanism of Neurotoxicity by a Serotonin–Acrolein Polymeric Melanoid

Document Type

Article

Publication Title

Neurotoxicity Research

Abstract

Postoperative cognitive dysfunction may be associated with the toxic products of lipid peroxidation, such as the α,β-unsaturated aldehyde acrolein, which accumulates in aging. We previously identified an acrolein-mediated, serotonin-derived melanoid product, or SDM. This study further characterizes this putative novel neuromelanin, which is not made from catecholamines. In addition to its strong protein-binding properties, we observed that SDM binds Fe(2+) readily and exhibits complex redox characteristics. SDM may exist as a two-dimensional network of polymers that coalesce into larger entities exhibiting electroactive properties. These observations suggest that SDM may contribute to the decline in cognition due to focal degeneration from SDM-mediated free-radical production. We know that inhalational anesthetics sequester acrolein, which is toxic to neurons, and we propose that the local increase in acrolein depletes serotonin levels and enhances neuronal vulnerability through the production of neuromelanin-like structures, such as SDM.

DOI

10.1007/s12640-010-9173-3

Publication Date

2-2011

Keywords

Acrolein, Inhaled anesthetics, Neuromelanin, Postoperative cognitive dysfunction, Serotonin

ISSN

1476-3524

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