D-Serine as a putative glial neurotransmitter

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• D-serine is increasingly recognized for its role as a neurotransmitter and neuromodulator.
• Astrocytic glia, particularly in brain regions rich in NMDA-glutamate receptors, synthesize D-serine.
• D-serine is a potent activator of the glycine site on NMDA receptors, surpassing glycine's potency.

Purpose of the Study:

• To elucidate the physiological role of D-serine in synaptic transmission.
• To investigate the mechanisms regulating D-serine release and its interaction with glutamate receptors.
• To explore the involvement of D-serine in neural development, specifically neuronal migration.

Main Methods:

• Investigated the effects of D-serine degradation by D-amino acid oxidase on NMDA neurotransmission.
• Examined the release of D-serine stimulated by glutamate acting on AMPA-glutamate receptors.
• Studied the interaction between glutamate-receptor-interacting protein, serine racemase, and D-serine release.
• Assessed the role of D-serine released from Bergmann glia in cerebellar neuron migration.

Main Results:

• Selective degradation of D-serine significantly impairs NMDA neurotransmission, while glycine degradation does not.
• Glutamate activation of AMPA-glutamate receptors on glia triggers D-serine release.
• Glutamate-receptor-interacting protein stimulates serine racemase activity, leading to D-serine release.
• D-serine released from Bergmann glia promotes the migration of cerebellar granule neurons.

Conclusions:

• D-serine is a critical co-agonist at NMDA receptors, with its release tightly regulated by glutamatergic signaling.
• D-serine plays a dual role in the central nervous system, modulating synaptic plasticity and guiding neuronal development.
• These findings highlight D-serine as a significant target for understanding and potentially treating neurological disorders.