Neuronal serine racemase regulates extracellular d-serine levels in the adult mouse hippocampus
- 419 Downloads
In the hippocampus of mice lacking the gene for serine racemase (SR), a d-serine synthesizing enzyme, in the CaMKIIα-expressing neurons, we observed a significant decrease in the extracellular concentration of d-serine, a coagonist for the N-methyl-d-aspartate type glutamate receptor (NMDAR), and NMDAR hypofunction as revealed by diminished extracellular taurine concentrations after an intra-hippocampal NMDA infusion when compared to the wild type controls. Therefore, the neuronal SR could regulate the extracellular d-serine signaling responsible for NMDAR activation in the hippocampus.
KeywordsCaMKIIα-expressing neurons Hippocampus In vivo microdialysis N-methyl-d-aspartate type glutamate receptor d-Serine Serine racemase
This work was supported by the CREST (Core Research for Evolutional Science and Technology) program funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan to TN research team including SI and AU. A postdoctoral National Research Service Award F32 MH090697 to DTB and grants R01MH05190 and P50MH0G0450 to JTC also supported this study. We thank the International Technology Exchange Society (an English editing agency: 3398 Tyler Drive Brunswick,OH 44212-3726 USA, Tel: 1-330-273-5409, Fax: 1-330-225-3834, E-mail: email@example.com) for their assistance in English editing for preparing our present manuscript, and are entirely responsible for the scientific content of this paper.
Conflict of interest
The authors declare that they have no conflict of interest.
The present experiments were performed in accordance with the guidance of the Tokyo Medical and Dental University and were approved by the Animal Investigation Committee of the Institution.
- Basu AC, Tsai GE, Ma CL, Ehmsen JT, Mustafa AK, Han L, Jiang ZI, Benneyworth MA, Froimowitz MP, Lange N, Snyder SH, Bergeron R, Coyle JT (2009) Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Mol Psychiatry 14:719–727. doi: 10.1038/mp.2008.130 PubMedCentralPubMedCrossRefGoogle Scholar
- Ishiwata S, Umino A, Umino M, Yorita K, Fukui K, Nishikawa T (2013b) Modulation of extracellular d-serine content by calcium permeable AMPA receptors in rat medial prefrontal cortex as revealed by in vivo microdialysis. Int J Neuropsychopharmacol 16:1395–1406. doi: 10.1017/S1461145712001484 PubMedCrossRefGoogle Scholar
- Paxinos G, Franklin K (2004) The mouse brain in stereotaxic coordinates, 2nd edn. Elsevier Academic Press, AmsterdamGoogle Scholar
- Rosenberg D, Artoul S, Segal AC, Kolodney G, Radzishevsky I, Dikopoltsev E, Foltyn VN, Inoue R, Mori H, Billard JM, Wolosker H (2013) Neuronal d-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity. J Neurosci 33(8):3533–3544. doi: 10.1523/JNEUROSCI.3836-12.2013 PubMedCrossRefGoogle Scholar