Serine Racemase Knockout Mice

Mori, Hisashi; Inoue, Ran

doi:10.1002/cbdv.200900293

Cited by 27 publications

(17 citation statements)

References 35 publications

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“…Because alteration of the D-Ser amount in the aged rat hippocampus was reported to be due to the decrease in the expression of SRR mRNA and protein (Turpin et al 2011), the present result using SRR -/-mice is reasonable. Moreover, SRR -/-mice were reported to have an impairment in learning and memory (Mori and Inoue 2010;Basu et al 2009); therefore, the present result provides useful information for wide utilization of SRR -/-mice in the pathological studies of neuronal diseases, including age-associated impairment.…”

Section: Discussionmentioning

confidence: 60%

Alteration of intrinsic amounts of d-serine in the mice lacking serine racemase and d-amino acid oxidase

et al. 2012

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For elucidation of the regulation mechanisms of intrinsic amounts of D-serine (D-Ser) which modulates the neuro-transmission of N-methyl-D-aspartate receptors in the brain, mutant animals lacking serine racemase (SRR) and D-amino acid oxidase (DAO) were established, and the amounts of D-Ser in the tissues and physiological fluids were determined. D-Ser amounts in the frontal brain areas were drastically decreased followed by reduced SRR activity. On the other hand, a moderate but significant decrease in D-Ser amounts was observed in the cerebellum and spinal cord of SRR knock-out (SRR(-/-)) mice compared with those of control mice, although the amounts of D-Ser in these tissues were low. The amounts of D-Ser in the brain and serum were not altered with aging. To clarify the uptake of exogenous D-Ser into the brain tissues, we have determined the D-Ser of SRR(-/-) mice after oral administration of D-Ser for the first time, and a drastic increase in D-Ser amounts in all the tested tissues was observed. Because both DAO and SRR are present in some brain areas, we have established the double mutant mice lacking SRR and DAO for the first time, and the contribution of both enzymes to the intrinsic D-Ser amounts was investigated. In the frontal brain, most of the intrinsic D-Ser was biosynthesized by SRR. On the other hand, half of the D-Ser present in the hindbrain was derived from the biosynthesis by SRR. These results indicate that the regulation of intrinsic D-Ser amounts is different depending on the tissues and provide useful information for the development of treatments for neuronal diseases.

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Section: Discussionmentioning

confidence: 60%

Alteration of intrinsic amounts of d-serine in the mice lacking serine racemase and d-amino acid oxidase

et al. 2012

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“…Because the mutant mice without the SR protein show a marked decrease in the expression level of D-serine (10–20% of WT mice) in the brain [33], [60], [61] and because D-serine distribution closely correlates with that of SR [2], [62], SR is a predominant enzyme for D-serine production [63]. Accordingly, SR has been considered an important enzyme for effective neurotransmission and synaptic plasticity via NMDAR activation.…”

Section: Discussionmentioning

confidence: 99%

Increased Sensitivity to Inflammatory Pain Induced by Subcutaneous Formalin Injection in Serine Racemase Knock-Out Mice

2014

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D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), is widely distributed in the central nervous system and is synthesized from L-serine by serine racemase (SR). NMDAR plays an important role in pain processing including central sensitization that eventually causes hyperalgesia. To elucidate the roles of D-serine and SR in pain transmission, we evaluated the behavioral changes and spinal nociceptive processing induced by formalin using SR knock-out (KO) mice. We found that SR is mainly distributed in lamina II of the dorsal horn of the spinal cord in wild-type (WT) mice. Although the formalin injected subcutaneously induced the biphasic pain response of licking in SR-KO and WT mice, the time spent on licking was significantly longer in the SR-KO mice during the second phase of the formalin test. The number of neurons immunopositive for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK), which are molecular pain markers, in laminae I-II of the ipsilateral dorsal horn was significantly larger in the SR-KO mice. Immunohistochemical staining revealed that the distribution of SR changed from being broad to being concentrated in cell bodies after the formalin injection. On the other hand, the expression level of the cytosolic SR in the ipsilateral dorsal horn significantly decreased. Oral administration of 10 mM D-serine in drinking water for one week cancelled the difference in pain behaviors between WT and SR-KO mice in phase 2 of the formalin test. These findings demonstrate that the SR-KO mice showed increased sensitivity to inflammatory pain and the WT mice showed translocation of SR and decreased SR expression levels after the formalin injection, which suggest a novel antinociceptive mechanism via SR indicating an important role of D-serine in pain transmission.

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“…These injections and ischemia result in overactivation of the NMDA receptors, and the KO mice had a decreased level of d-serine, which protected against this overstimulation. Mori and Inoue [8] have summarized the similarities and differences between these three strains of KO mice in their recent review. They note that some behavioral differences may be caused by differences in the genetic background of the mice.…”

Section: Serine Racemase (Ec 51118)mentioning

confidence: 99%

“…dSerine, which is synthesized by serine racemase and degraded by d-amino-acid oxidase, binds to the coagonist binding site of the N-methyl-d-aspartate (NMDA)-subtype of glutamate receptors and modulates NMDA receptor activity. The NMDA receptors are involved in numerous physiological and pathological processes, including synaptic plasticity, learning, memory, neuronal cell migration, and neural disease [8,9].…”

Section: Introductionmentioning

confidence: 99%

d-Amino acid metabolism in mammals: Biosynthesis, degradation and analytical aspects of the metabolic study

Ohide

Miyoshi

Maruyama

et al. 2011

Journal of Chromatography B

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Serine Racemase Knockout Mice

Cited by 27 publications

References 35 publications

Alteration of intrinsic amounts of d-serine in the mice lacking serine racemase and d-amino acid oxidase

Alteration of intrinsic amounts of d-serine in the mice lacking serine racemase and d-amino acid oxidase

Increased Sensitivity to Inflammatory Pain Induced by Subcutaneous Formalin Injection in Serine Racemase Knock-Out Mice

d-Amino acid metabolism in mammals: Biosynthesis, degradation and analytical aspects of the metabolic study

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