Cellular distribution of d-serine, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelia

Glutamate is the main neurotransmitter at the synapses between sensory cells and primary afferents in the peripheral vestibular system. Evidence has recently been obtained demonstrating that the atypical amino acid d-serine is the main endogenous co-agonist of the N-methyl-d-aspartate receptors in the CNS. We studied the distribution of d-serine and its synthesizing and degrading enzymes, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelium using immunocytochemistry. d-Serine, serine racemase and d-amino acid oxidase were localized in the transitional cells, which are parasensory cells located between the sensory epithelium and the dark cells. The dark cells expressed only serine racemase. d-Serine was also detected in the supporting cells of the sensory epithelium. These cells, which are in close contact with glutamatergic synapses, express GLAST, a glial specific transporter for glutamate. They may have similar functions to glial cells in the CNS and thus expression of d-serine suggests a neuromodulator role for d-serine at the glutamatergic synapses in the peripheral vestibular system. Our data also indicate that the metabolism of d-serine is not restricted to glial cells suggesting that the amino acid may play an additional role in the peripheral nervous system

D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels

Astrocytes are involved in chemoreception in brainstem areas that regulate breathing rhythm, and astrocytes are known to release d-serine. Here the authors show that astrocyte release of d-serine contributes to CO2 sensing and breathing in brainstem slices, and in vivo in awake unrestrained mice