Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4351080 | Neuroscience Letters | 2006 | 4 Pages |
Abstract
d-Serine is an endogenous coagonist that increases the opening of N-methyl-d-aspartate (NMDA)-type glutamate receptor channels. We previously reported a reduction of d-serine serum levels in schizophrenia, supporting the disease hypothesis of NMDA receptor-mediated hypo-neurotransmission. The serum levels of d-serine are thought to reflect brain d-serine content. It is important to understand whether there is a direct link between the altered d-serine levels and NMDA receptor expression in vivo or whether these are independent processes. Two polymorphisms are known to regulate the expression of NMDA receptor subunit genes: (GT)n (rs3219790) in the promoter region of the NR2A subunit gene (GRIN2A) and â200T>G (rs1019385) in the NR2B gene (GRIN2B). These polymorphisms are also reported to be associated with schizophrenia. Therefore, we examined the correlation between these two polymorphisms and d-serine serum levels in mentally healthy controls, schizophrenics and the combined group. We observed no significant genotype-phenotype correlations in any of the sample groups. However, analyses of larger sample numbers and the detection of additional polymorphisms that affect gene expression are needed before we can conclude that NMDA receptor expression and serum levels of d-serine, if involved in schizophrenia pathophysiology, are independent and additive events.
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Authors
Yoshimi Iwayama, Kenji Hashimoto, Mizuho Nakajima, Tomoko Toyota, Kazuo Yamada, Eiji Shimizu, Masanari Itokawa, Akinori Hoshika, Masaomi Iyo, Takeo Yoshikawa,