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The alterations of glutamate transporter 1 and glutamine synthetase in the rat brain of a learned helplessness model of depression

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Abstract

Background

Although glutamate transmission via astrocytes has been proposed to contribute to the pathophysiology of depression, the precise mechanisms are unknown. Herein, we investigated the levels of glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) of astrocytes in learned helplessness (LH) rats (an animal model of depression) and non-LH rats (an animal model of resilience).

Methods

We administered inescapable mild electric shock to rats and then discriminated the LH and non-LH rats by a post-shock test. Almost 55% of the rats acquired LH. We then measured the expressions of GLT-1 and GS in several brain regions of LH and non-LH rats by Western blot analysis.

Results

The levels of GLT-1 and GS in the CA-1, CA-3, dentate gyrus (DG), medial prefrontal cortex (mPF), and nucleus accumbens (NAc) of the LH group were significantly higher than those of the control group. The GS levels in the amygdala of the LH rats were significantly decreased compared to the controls. There were significant differences in GLT-1 and GS levels between the non-LH and LH rats in the CA-1 and CA-3.

Conclusions

These results suggest that the LH rats experienced up-regulations of GLT-1 and GS in the CA-1, CA-3, DG, mPF, and NAc and a down-regulation of GS in the amygdala. It is possible that the effects of the GLT-1 and GS levels on astrocytes in the CA-1 and CA-3 are critical for the differentiation of resilience from vulnerability.

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Acknowledgments

We thank Miwako Nakamura (Chiba University Graduate School of Medicine) for her technical support with the general experiments.

Funding

This research received no specific grant from any funding agency or commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuou-ku, Chiba, Chiba, 260-8670, Japan

    Kouhei Yoshino, Yasunori Oda, Makoto Kimura, Hiroshi Kimura, Masahito Nangaku & Masaomi Iyo

  2. Department of Psychiatry, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba, 290-0111, Japan

    Yukihiko Shirayama

Authors
  1. Kouhei Yoshino
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  2. Yasunori Oda
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  3. Makoto Kimura
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  4. Hiroshi Kimura
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  5. Masahito Nangaku
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  6. Yukihiko Shirayama
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  7. Masaomi Iyo
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Contributions

Conceived and designed the experiments: K.Y., Y.O., M.K., H.K., M.N., Y.S., M.I. Performed the experiments: K.Y., Y.O., M.K., M.N. Analyzed the data: K.Y., Y.O., M.K. Wrote the paper: K.Y., Y.O., M.K., Y.S. Supervised the research: Y.S., M.I.

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Correspondence to Yasunori Oda.

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Yoshino, K., Oda, Y., Kimura, M. et al. The alterations of glutamate transporter 1 and glutamine synthetase in the rat brain of a learned helplessness model of depression. Psychopharmacology 237, 2547–2553 (2020). https://doi.org/10.1007/s00213-020-05555-3

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  • DOI: https://doi.org/10.1007/s00213-020-05555-3

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