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Increased Levels of Monoamine-Derived Potential Neurotoxins in Fetal Rat Brain Exposed to Ethanol

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Abstract

Pregnant SD rats were exposed to ethanol (25 % (v/v) ethanol at 1.0, 2.0 or 4.0 g/kg body weight from GD8 to GD20) to assess whether ethanol-derived acetaldehyde could interact with endogenous monoamine to generate tetrahydroisoquinoline or tetrahydro-beta-carboline in the fetuses. The fetal brain concentration of acetaldehyde increased remarkably after ethanol administration (2.6 times, 5.3 times and 7.8 times as compared to saline control in 1.0, 2.0 and 4.0 g/kg ethanol-treated groups, respectively) detected by HPLC with 2,4-dinitrophenylhydrazine derivatization. Compared to control, ethanol exposure induced the formation of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal), N-methyl-salsolinol (NMSal) and 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (6-OH-MTHBC) in fetal rat brains. Determined by HPLC with electrochemical detector, the levels of dopamine and 5-hydroxytryptamine in whole fetal brain were not remarkably altered by ethanol treatment, while the levels of homovanillic acid and 5-hydroxyindole acetic acid in high dose (4.0 g/kg) of ethanol-treated rats were significantly decreased compared to that in the control animals. 4.0 g/kg ethanol administration inhibited the activity of mitochondrial monoamine oxidase (51.3 % as compared to control) and reduced the activity of respiratory chain complex I (61.2 % as compared to control). These results suggested that ethanol-induced alteration of monoamine metabolism and the accumulation of dopamine-derived catechol isoquinolines and 5-hydroxytryptamine-derived tetrahydro-beta-carbolines may play roles in the developmental dysfuction of monoaminergic neuronal systems.

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Acknowledgments

The authors thank the support from the Ministry of Industry and Information, China (No. A2220060002), and partially support from the Presidential Science and Technology Development Foundation of ZTRI, China (No. 412011CA0280).

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Authors and Affiliations

  1. School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, People’s Republic of China

    Jian Mao, Hong Ma, Yan Xu, Yang Su, Huiyang Zhu, Rui Wang, Fankai Lin, Hong Qing & Yulin Deng

  2. Zhengzhou Tobacco Research Institute of China National Tobacco Corporation, 2 Fengyang Street, High-tech Industrial Development Zone, Zhengzhou, 450001, People’s Republic of China

    Jian Mao

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  1. Jian Mao
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Correspondence to Yulin Deng.

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Jian Mao, Hong Ma and Yan Xu contributed equally to this work.

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Mao, J., Ma, H., Xu, Y. et al. Increased Levels of Monoamine-Derived Potential Neurotoxins in Fetal Rat Brain Exposed to Ethanol. Neurochem Res 38, 356–363 (2013). https://doi.org/10.1007/s11064-012-0926-7

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