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Increase in Glutamatergic Terminals in the Striatum Following Dopamine Depletion in a Rat Model of Parkinson’s Disease

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Dopaminergic neuron degeneration is known to give rise to dendrite injury and spine loss of striatal neurons, however, changes of intrastriatal glutamatergic terminals and their synapses after 6-hydroxydopamine (6OHDA)-induced dopamine (DA)-depletion remains controversial. To confirm the effect of striatal DA-depletion on the morphology and protein levels of corticostriatal and thalamostriatal glutamatergic terminals and synapses, immunohistochemistry, immuno-electron microscope (EM), western blotting techniques were performed on Parkinson’s disease rat models in this study. The experimental results of this study showed that: (1) 6OHDA-induced DA-depletion resulted in a remarkable increase of Vesicular glutamate transporter 1 (VGlut1) + and Vesicular glutamate transporter 2 (VGlut2)+ terminal densities at both the light microscope (LM) and EM levels, and VGlut1+ and VGlut2+ terminal sizes were shown to be enlarged by immuno-EM; (2) Striatal DA-depletion resulted in a decrease in both the total and axospinous terminal fractions of VGlut1+ terminals, but the axodendritic terminal fraction was not significantly different from the control group. However, total, axospinous and axodendritic terminal fractions for VGlut2+ terminals declined significantly after striatal DA-depletion. (3) Western blotting data showed that striatal DA-depletion up-regulated the expression levels of the VGlut1 and VGlut2 proteins. These results suggest that 6OHDA-induced DA-depletion affects corticostriatal and thalamostriatal glutamatergic synaptic inputs, which are involved in the pathological process of striatal neuron injury induced by DA-depletion.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81471288), and by the National Key R&D Program of China (Grant No. 2017YFA0104704).

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  1. Xuefeng Zheng and Ziyun Huang have contributed equally to this article.

Authors and Affiliations

  1. Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Xuefeng Zheng, Ziyun Huang, Yaofeng Zhu, Zhi Chen, Tao Chen, Linju Jia, Yanmei Li & Wanlong Lei

  2. Institute of Medicine, College of Medicine, Jishou University, Jishou, China

    Yaofeng Zhu

  3. Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, China

    Bingbing Liu

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  1. Xuefeng Zheng
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Zheng, X., Huang, Z., Zhu, Y. et al. Increase in Glutamatergic Terminals in the Striatum Following Dopamine Depletion in a Rat Model of Parkinson’s Disease. Neurochem Res 44, 1079–1089 (2019). https://doi.org/10.1007/s11064-019-02739-y

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