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Effects of 2‐Chloroethyl Ethyl Sulfide (CEES) on the Dopaminergic System in Guinea Pig Brain
Author(s) -
GadsdenGray Jessica,
Mukherjee Shyamali,
Das Salil K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.749.4
Mustard gas is a chemical warfare agent used in World Wars I and II, the Gulf War, and on civilian occupants of the Iranian village of Halabja. Inhalation of sulfur mustard causes hemorrhagic inflammation of the tracheobronchial tree in addition to severe pulmonary complications such as adult respiratory distress syndrome (ARDS). Studies conducted with the mustard gas analog 2‐chloroethyl ethyl sulfide (CEES) have indicated that its inhalation is able not only to cause significant lung damage, but also to cause it to cross the blood brain‐barrier. CEES is known to decrease the antioxidant defense systems and increase lipid peroxidation in the brain; however, the molecular mechanisms of this process remain unclear. The purpose of this study was to determine if intratracheal CEES infusion caused abnormality in the dopaminergic system in guinea pigs. Western blotting and immunohistochemical studies were performed to examine the expression of alpha‐synuclein, the dopamine transporter, dopamine D2 receptors, and tyrosine hydroxylase. Our results show that intratracheal CEES infusion caused increased expression of dopamine D2 receptors and tyrosine hydroxylase, down‐regulation of the dopamine transporter, and increased alpha‐synuclein expression leading to neurotoxicity in the guinea pig model, which may be mediated by oxidative stress. This research was supported by grants from the Department of the Army(W81XWH‐06‐2‐0044) and NIH(5T32HL007735‐12).