| First Author | Osaki A | Year | 2023 |
| Journal | Biochem Biophys Res Commun | Volume | 641 |
| Pages | 186-191 | PubMed ID | 36535077 |
| Mgi Jnum | J:332661 | Mgi Id | MGI:7428177 |
| Doi | 10.1016/j.bbrc.2022.12.037 | Citation | Osaki A, et al. (2023) Endogenous d-serine exists in the mammalian brain independent of synthesis by serine racemase. Biochem Biophys Res Commun 641:186-191 |
| abstractText | Activation of N-methyl-(d)-aspartate receptors (NMDARs) requires binding of a co-agonist in addition to (l-)glutamate. (d-)serine binds to the co-agonist site on GluN1 subunits of NMDARs and modulates glutamatergic neurotransmission. While loss of GluN1 subunits in mice results in neonatal death due to respiratory failure, animals that lack a (d-)serine synthetic enzyme, serine racemase (SR), show grossly normal growth. However, SR-independent origins of (d-)serine in the brain remain unclarified. In the present study, we investigated the origin of brain (d-)serine in mice. Loss of SR significantly reduced (d-)serine in the cerebral cortex, but a portion of (d-)serine remained in both neonates and adults. Although (d-)serine was also produced by intestinal bacteria, germ-free experiments did not influence (d-)serine levels in the cerebral cortex. In addition, treatment of SR-knockout mice with antibiotics showed a significant reduction of intestinal (d-)serine, but no reduction in the brain. On the other hand, restriction of dietary intake reduced systemic circulation of (d-)serine and resulted in a slight decrease of (d-)serine in the cerebral cortex, but did not account for brain (d-)serine found in the SR-knockout mice. Therefore, our findings show that endogenous (d-)serine of non-SR origin exists in the brain. Such previously unrecognized, SR-independent, endogenous (d-)serine may contribute baseline activity of NMDARs, especially in developing brain, which has minimal SR expression. |
