Expression of <Emphasis Type="SmallCaps">l</Emphasis>-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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Authors: | Gye Sun Jeon Deok Hyung Choi Ha Na Lee Dong Woon Kim Chun Kee Chung Sa Sun Cho |
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Institution: | (1) Department of Anatomy, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, South Korea;(2) Department of Anatomy, Chungnam National University College of Medicine, Daejeon, South Korea;(3) Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea;(4) Neuroscience Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea |
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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.
G. S. Jeon and D. H. Choi contributed equally to this work. |
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Keywords: | Phgdh ASCT1 Kainic acid Astrocyte l-Serine" target="_blank">l-Serine Immunohistochemistry |
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