D-
Serine is known to be essential for the activation of the
N-methyl-D-aspartate (
NMDA) receptor in the excitation of glutamatergic neurons, which have critical roles in long-term potentiation and memory formation. D-
Serine is also thought to be involved in
NMDA receptor-mediated neurotoxicity. The deletion of
serine racemase (SRR), which synthesizes D-
serine from
L-serine, was recently reported to improve ischemic damage in mouse
middle cerebral artery occlusion model. However, the cell type in which this phenomenon originates and the regulatory mechanism for D-/
L-serine remain elusive. The D-/
L-serine content in ischemic brain increased until 20 hours after recanalization and then leveled off gradually. The results of in vitro experiments using cultured cells suggested that D-
serine is derived from neurons, while
L-serine seems to be released from astroglia. Immunohistochemistry studies of brain tissue after
cerebral ischemia showed that SRR is expressed in neurons, and
3-phosphoglycerate dehydrogenase (3-PGDH), which synthesizes
L-serine from
3-phosphoglycerate, is located in astrocytes, supporting the results of the in vitro experiments. A western blot analysis showed that neither SRR nor 3-PGDH was upregulated after
cerebral ischemia. Therefore, the increase in D-/
L-serine was not related to an increase in SRR or 3-PGDH, but to an increase in the substrates of SRR and 3-PGDH.