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Opposite effects of α-lipoic acid on antioxidation and long-term potentiation in control and chronically lead-exposed rats

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Abstract

Among the developmental changes identified in rats exposed to lead are impairments in long-term potentiation (LTP) in the hippocampus and changes in the levels of reactive oxygen species (ROS) in cells and some soft tissues. α-Lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced oxidative stress. To explore the effects of LA on LTP in chronically lead-exposed rats and the relationship between ROS and LTP in both control and lead-exposed rats, we have compared LTP and oxidative stress parameters in groups of lead-exposed and control rats with or without LA treatment (10, 25, 50, and 100 mg/kg through intraperitoneal injection). The capacity of LA to decrease hippocampal lead levels in lead-exposed rats was examined. We found that LA had no effects in decreasing the level of lead in the hippocampus, but it did appear to have both antioxidant properties and a reparatory effect on LTP amplitude in rats developmentally exposed to lead for 2 weeks following birth. Interestingly, bell-shaped dose-response curves emerged. In the lower LA dosage groups (10, 25 mg/kg LA), there was an increasing LTP amplitude. The strongest protective effect in terms of the induction and amplitude of LTP in the lead-exposed group with at 25 mg/kg LA; when higher dosages were applied (50, 100 mg/kg LA), the LTP amplitude decreased as compared to the 25 mg/kg LA treatment group. The administration of LA to control animals resulted in a significant impairment of LTP amplitude, with the 100 mg/kg LA treatment having harmful effects on the oxidative parameters. These differential effects of LA on LTP in control and lead-exposed rats may be due to the different redox status of the control and lead-exposed rats.

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Abbreviations

EPSPs:

excitatory postsynaptic potentials

GSH:

glutathione

LA:

lipoic acid

LTP:

long-term potentiation

MDA:

malondialdehyde

ROS:

reactive oxygen species

T-SOD:

total superoxide dismutase

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2002CB512907), the National Nature Science Foundation of China (No. 30630057; 30670554; 30670662; 30672290), Academia Sinica (No. KZCX3-SW-437), China Postdoctoral Science Foundation (No. 20060400719) and K.C. Wong Education Foundation of Hong Kong.

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Authors and Affiliations

  1. Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China

    Hui-Li Wang, Xiang-Tao Chen, Shu-Ting Yin, Jin Liu, Ming-Liang Tang, Chuan-Yun Wu & Di-Yun Ruan

  2. Institute of Polar Environment, University of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China

    Hui-Li Wang

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  1. Hui-Li Wang
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Correspondence to Di-Yun Ruan.

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Wang, HL., Chen, XT., Yin, ST. et al. Opposite effects of α-lipoic acid on antioxidation and long-term potentiation in control and chronically lead-exposed rats. Naunyn-Schmied Arch Pharmacol 378, 303–310 (2008). https://doi.org/10.1007/s00210-008-0307-6

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