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Expression of l-Serine Biosynthetic Enzyme 3-Phosphoglycerate Dehydrogenase (Phgdh) and Neutral Amino Acid Transporter ASCT1 Following an Excitotoxic Lesion in the Mouse Hippocampus

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Abstract

The nonessential amino acid l-serine functions as a glia-derived trophic factor and strongly promotes the survival and differentiation of cultured neurons. The l-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase (Phgdh) and the small neutral amino acid transporter ASCT1 are preferentially expressed in specific glial cells in the brain. However, their roles in pathological progression remain unclear. We examined the expression of Phgdh and ASCT1 in kainic acid (KA)-induced neurodegeneration of the mouse hippocampus using immunohistochemistry and Western blots. Our quantitative analysis revealed that Phgdh and ASCT1 were constitutively expressed in the normal brain and transiently upregulated by KA-treatment. At the cellular level, Phgdh was expressed in astrocytes in control and in KA-treated mice while ASCT1 that was expressed primarily in the neurons of the normal brain appeared also in activated astrocytes in KA treated mouse brain. The preferential glial expression of ASCT1 was consistent with that of Phgdh. These results demonstrate injury-induced changes in Phgdh and ASCT1 expression. It is hypothesized that the secretion of l-serine is regulated by astrocytes in response to toxic molecules such as glutamate and free radicals that promote neurodegeneration, and may correspond to the level of l-serine needed for neuronal survival and glial activation during brain insults.

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Acknowledgments

This study was supported by the second stage Brain Korea 21 Project in 2008, a grant (M103KV010018 04K2201 01850) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea, a grant no. 04-2007-076 from the Seoul National University Hospital Research Fund. The authors thank Dr. M. Watanabe, Hokkaido University School of Medicine, Japan, for the Phgdh antibody.

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Authors and Affiliations

  1. Department of Anatomy, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, South Korea

    Gye Sun Jeon, Deok Hyung Choi, Ha Na Lee & Sa Sun Cho

  2. Department of Anatomy, Chungnam National University College of Medicine, Daejeon, South Korea

    Dong Woon Kim

  3. Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea

    Chun Kee Chung

  4. Neuroscience Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea

    Sa Sun Cho

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  1. Gye Sun Jeon
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  2. Deok Hyung Choi
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Correspondence to Sa Sun Cho.

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G. S. Jeon and D. H. Choi contributed equally to this work.

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Jeon, G.S., Choi, D.H., Lee, H.N. et al. Expression of l-Serine Biosynthetic Enzyme 3-Phosphoglycerate Dehydrogenase (Phgdh) and Neutral Amino Acid Transporter ASCT1 Following an Excitotoxic Lesion in the Mouse Hippocampus. Neurochem Res 34, 827–834 (2009). https://doi.org/10.1007/s11064-008-9831-5

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  • DOI: https://doi.org/10.1007/s11064-008-9831-5

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