D-Serine's Journey Between Stars and Synapses.
Sarah Mountadem1, Stéphane Henri Richard Oliet1, Aude Panatier2
1Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000, Bordeaux, France.
Neurochemical Research
|October 14, 2025
Summary
Astrocytes release D-serine, a key gliotransmitter that modulates NMDA receptor activity, synaptic plasticity, and memory. Impaired D-serine synthesis in astrocytes may contribute to cognitive deficits in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Astrocytes are crucial glial cells regulating synaptic transmission.
- D-serine is a key gliotransmitter influencing NMDA receptor (NMDAR) function.
- Astrocytic D-serine impacts cognitive processes and NMDAR-dependent functions.
Purpose of the Study:
- To review the multifaceted role of astrocytic D-serine.
- To highlight findings on D-serine's regulation of NMDAR activity, synaptic plasticity, and memory.
- To discuss the implications of impaired D-serine synthesis in neurodegenerative disorders.
Main Methods:
- Review of existing literature and laboratory findings spanning two decades.
- Investigation of astrocyte-neuron communication pathways.
- Analysis of D-serine's role in synaptic cleft dynamics and cognitive function.
Main Results:
- Astrocytic D-serine dynamically controls NMDAR activity and long-term synaptic plasticity.
- Astrocytic morphological plasticity, intracellular Ca2+, and specific receptors (CB1, EphB3) influence D-serine availability.
- Impaired astrocytic D-serine synthesis affects co-agonist availability and cognitive functions.
Conclusions:
- Astrocytic D-serine is vital for astrocyte-neuron communication.
- D-serine plays a significant role in higher-order brain functions, including memory.
- Dysregulation of astrocytic D-serine is implicated in cognitive impairments in diseases like Alzheimer's.
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