Toxicity of a serotonin-derived neuromelanin.
Postoperative Cognitive Dysfunction (POCD) is associated with increased mortality in the elderly and may occur from lipid peroxidation in aging. We previously showed that sevoflurane sequesters acrolein, which promotes the formation of a novel species of a putative neuromelanin. The current study examined the properties of this serotonin-derived melanoid (SDM). The interaction of SDM with unilamellar vesicles (ULVs) was examined using lipid membrane probes. Vesicle disruption was investigated by leakage of dye from calcein-loaded ULVs. We observed that SDM decreased diphenyl-hexatriene fluorescence anisotropy and increased the temperature-dependent change in anisotropy. SDM changed the absorbance of merocyanin-bound ULVs. SDM increased detergent-mediated calcein leakage. SDM structure was dramatically altered upon interaction with ULVs. We also observed that SDM enhanced detergent-mediated leakage of loaded ULVs, suggesting that SDM may be neurotoxic. We propose that inhalational agents, which sequester acrolein, may promote the production of certain species of neuromelanin that depletes local serotonin and enhances neuronal vulnerability.
Miller
Elizabeth D
ED
Department of Anesthesiology, University of Missouri - Kansas City School of Medicine, 4401 Wornall Road, Kansas City, MO 64111, USA.
Fibuch
Eugene E
EE
Seidler
Norbert W
NW
D000171:Acrolein / Q000378:metabolism; D016880:Anisotropy; D003072:Cognition Disorders / Q000378:metabolism*; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000096:biosynthesis / Q000633:toxicity*; D011183:Postoperative Complications / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D053835:Unilamellar Liposomes
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008543:Melanins; D053835:Unilamellar Liposomes; C014121:neuromelanin; D012701:Serotonin; D000171:Acrolein; C007740:fluorexon