Polymorphism in the 5′-promoter region of serine racemase gene in schizophrenia

Goltsov, A Y; Loseva, J G; Andreeva, Tatiana V.; Grigorenko, Anastasia P.; Абрамова, Л. И.; Каледа, В. Г.; Орлова, В. С.; Moliaka, Yuri K.; Rogaev, Evgeny I.

doi:10.1038/sj.mp.4001801

Cited by 49 publications

(27 citation statements)

References 8 publications

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“…Although genetic linkage studies have not associated polymorphisms in the NMDAR to schizophrenia (Martucci et al 2003;Rice et al 2001), there are a number of studies that have implicated genes that specifically modulate the NMDAR glycine binding site. These include D-amino acid oxidase and G72, which are involved in D-serine catabolism, and the D-serine synthesis enzyme, serine racemase (Chumakov et al 2002;Goltsov et al 2006;Morita et al 2006;Schumacher et al 2004). Morita et al (2006) found that a SNP associated with a 60% reduction in serine racemase promoter function was significantly elevated in patients with schizophrenia.…”

Section: Discussionmentioning

confidence: 98%

Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia

2008

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Section: Discussionmentioning

confidence: 98%

Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia

2008

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“…The decreased in vivo radioligand binding to the PCP site within the ion channel of the NMDA receptor of the hippocampus of schizophrenic patients could be a consequence of the reduced open frequency of the ion channel due to diminution of d-serine or glycine signaling [126]. Moreover, significant association between schizophrenia and single nucleotide polymorphisms (SNPs) and/or haplotypes of DAO [127] and serine racemase [128,129], and the expressional changes in the protein products or mRNAs of these genes in the postmortem brains of patients with schizophrenia, have been reported [130][131][132][133], although other studies fail to replicate these data [134][135][136].…”

Section: Schizophreniamentioning

confidence: 97%

Analysis of free d-serine in mammals and its biological relevance

Nishikawa

2011

Journal of Chromatography B

134

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“…A less robust but replicated finding suggests that serine racemase (SZGene rank #45) itself may be a risk gene for schizophrenia (Morita et al 2007). A single nucleotide polymorphism is the 5′ promoter region of the gene is associated with schizophrenia and results in reduced expression of serine racemase (Goltsov et al 2006). This would result in reduced D-serine levels and consequent NMDAR hypofunction.…”

Section: Schizophrenia Risk Genes and Glutamatergic Neurotransmissionmentioning

confidence: 99%

Glutamatergic Synaptic Dysregulation in Schizophrenia: Therapeutic Implications

Coyle

Basu

Benneyworth

et al. 2012

Handbook of Experimental Pharmacology

157

100

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Schizophrenia affects approximately 1% of the population and continues to be associated with poor outcome because of the limited efficacy of and noncompliance with existing antipsychotic medications. An alternative hypothesis invoking the excitatory neurotransmitter, glutamate, arose out of clinical observations that NMDA receptor antagonists, the dissociative anesthetics like ketamine, can replicate in normal individuals the full range of symptoms of schizophrenia including psychosis, negative symptoms, and cognitive impairments. Low dose ketamine can also re-create a number of physiologic abnormalities characteristic of schizophrenia. Postmortem studies have revealed abnormalities in endogenous modulators of NMDA receptors in schizophrenia as well as components of a postsynaptic density where NMDA receptors are localized. Gene association studies have revealed several genes that affect NMDA receptor function whose allelic variants are associated with increased risk for schizophrenia including genes encoding D-amino acid oxidase, its modulator G72, dysbindin, and neuregulin. The parvalbumin-positive, fast-firing GABAergic interneurons that provide recurrent inhibition to cortical-limbic pyramidal neurons seem to be most sensitive to NMDA receptor hypofunction. As a consequence, disinhibition of glutamatergic efferents disrupts cortical processing, causing cognitive impairments and negative symptoms, and drives subcortical dopamine release, resulting in psychosis. Drugs designed to correct the cortical-limbic dysregulated glutamatergic neurotransmission show promise for reducing negative and cognitive symptoms of schizophrenia as well as its positive symptoms.

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Polymorphism in the 5′-promoter region of serine racemase gene in schizophrenia

Cited by 49 publications

References 8 publications

Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia

Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia

Analysis of free d-serine in mammals and its biological relevance

Glutamatergic Synaptic Dysregulation in Schizophrenia: Therapeutic Implications

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