Serine racemase is predominantly localized in neurons in mouse brain

Journal of Comparative Neurology - Tập 510 Số 6 - Trang 641-654 - 2008
Kazushi Miya1,2,3, Ran Inoue1,3, Yoshimi Takata1, Manabu Abe4, Rie Natsume4, Kenji Sakimura4, Kazuhisa Hongou2, Toshio Miyawaki2, Hisashi Mori1
1Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan
2Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
3The first two authors contributed equally to this work.
4Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan

Tóm tắt

AbstractD‐Serine is the endogenous ligand for the glycine binding site of the N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptor (GluR) channel and is involved in the regulation of synaptic plasticity, neural network formation, and neurodegenerative disorders. D‐Serine is synthesized from L‐serine by serine racemase (SR), which was first reported to be localized in astrocytes. However, recently, SR mRNA and its protein have been detected in neurons. In this study, we examined the SR distribution in the brain during postnatal development and in cultured cells by using novel SR knockout mice as negative controls. We found that SR is predominantly localized in pyramidal neurons in the cerebral cortex and hippocampal CA1 region. Double immunofluorescence staining revealed that SR signals colocalized with those of the neuron‐specific nuclear protein, but not with the astrocytic markers glial fibrillary acid protein and 3‐phosphoglycerate dehydrogenase. In the striatum, we observed SR expression in γ‐aminobutyric acid (GABA)ergic medium‐spiny neurons. Furthermore, in the adult cerebellum, we detected weak but significant SR signals in GABAergic Purkinje cells. From these findings, we conclude that SR is expressed predominantly in many types of neuron in the brain and plays a key role in the regulation of brain functions under physiological and pathological conditions via the production of the neuromodulator D‐serine. J. Comp. Neurol. 510:641–654, 2008. © 2008 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1038/361031a0

10.1074/jbc.M111814200

10.1196/annals.1300.020

10.1073/pnas.222421299

10.1016/j.molbrainres.2004.10.027

10.1074/jbc.M110793200

10.1074/jbc.M405726200

10.1074/jbc.275.13.9690

10.1111/j.1460-9568.2006.05081.x

10.1111/j.1471-4159.1993.tb03219.x

10.1016/j.ejphar.2006.09.062

10.1016/0361-9230(87)90076-1

10.1176/ajp.148.10.1301

10.1074/jbc.M512927200

10.1124/jpet.104.070912

10.1073/pnas.0409723102

10.1016/0006-8993(88)91138-9

10.1006/bbrc.2001.4492

10.1126/science.2841759

10.1126/science.8096653

10.1016/S0079-6123(08)60446-X

10.1016/j.neulet.2004.01.014

10.1016/j.neures.2007.01.004

10.1111/j.1471-4159.2006.03835.x

10.1046/j.1460-9568.2003.02698.x

10.1073/pnas.97.9.4926

10.1073/pnas.0408483102

10.1242/dev.116.1.201

10.1073/pnas.0611620104

10.1111/j.1460-9568.2004.03768.x

10.1016/S0022-3956(99)00029-1

10.1016/j.cell.2006.02.051

10.1073/pnas.091002298

Philpot BD, 1997, Experience‐dependent modifications in MAP2 phosphorylation in rat olfactory bulb, J Neurosci, 17, 9596, 10.1523/JNEUROSCI.17-24-09596.1997

10.1002/cne.21016

10.1074/jbc.M311103200

10.1038/sj.emboj.7601840

10.1523/JNEUROSCI.17-05-01604.1997

10.1073/pnas.92.9.3948

10.1523/JNEUROSCI.3190-05.2005

Steffek AE, 2006, Serine racemase protein expression in cortex and hippocampus in schizophrenia, Neuroreport, 31, 1181, 10.1097/01.wnr.0000230512.01339.72

10.1016/S0006-291X(02)00321-2

10.1016/S0006-3223(98)00279-0

10.1523/JNEUROSCI.19-23-10318.1999

10.1523/JNEUROSCI.0448-07.2007

10.1111/j.1460-9568.2007.05769.x

Wang LZ, 2003, Spatiotemporal relationships among D‐serine, serine racemase, and D‐amino acid oxidase during mouse postnatal development, Acta Pharmacol Sin, 24, 965

10.1111/j.1460-9568.2005.04431.x

10.1073/pnas.96.23.13409

10.1016/S0197-0186(02)00055-4

10.1196/annals.1332.009

10.1186/1742-2094-1-2

10.1016/j.molbrainres.2004.03.007

10.1046/j.0953-816x.2001.01580.x

10.1523/JNEUROSCI.21-19-07691.2001

10.1073/pnas.2431073100

10.1679/aohc.70.127

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Journal of Comparative Neurology

Tập 510 Số 6

641-654

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