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Published on: September 16, 2022
D-serine in the developing human central nervous system
Sabine A Fuchs1, Lambertus Dorland, Monique G de Sain-van der Velden
1Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. s.fuchs@umcutrecht.nl
Insights
D-serine is crucial for human brain development, with levels highest at birth in healthy children. Deficiencies in D-serine impact brain development, but prenatal treatment may normalize levels and outcomes.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- D-serine is an amino acid found in the central nervous system.
- Its precise role in human brain development is not fully understood.
- 3-phosphoglycerate dehydrogenase deficiency impairs L-serine biosynthesis, potentially affecting D-serine levels.
Purpose of the Study:
- To investigate the role of D-serine in the human central nervous system.
- To analyze D-serine, L-serine, and glycine concentrations in cerebrospinal fluid.
- To compare levels between healthy children and those with 3-phosphoglycerate dehydrogenase deficiency.
Main Methods:
- Cerebrospinal fluid samples were collected from healthy children and children with 3-phosphoglycerate dehydrogenase deficiency.
- Concentrations of D-serine, L-serine, and glycine were measured.
- Levels were analyzed in relation to age and treatment status.
Main Results:
- Healthy newborns exhibited high D-serine concentrations, which decreased with age.
- D-serine levels were nearly undetectable in untreated patients with 3-phosphoglycerate dehydrogenase deficiency.
- A prenatally treated patient showed near-normal D-serine levels at birth and normal clinical phenotype.
Conclusions:
- D-serine plays a critical role in normal human brain development.
- D-serine deficiency is associated with aberrant brain development.
- Early intervention, potentially prenatal, may be crucial for managing D-serine related developmental disorders.
Abstract:
To elucidate the role of D-serine in human central nervous system, we analyzed D-serine, L-serine, and glycine concentrations in cerebrospinal fluid of healthy children and children with a defective L-serine biosynthesis (3-phosphoglycerate dehydrogenase deficiency). Healthy children showed high D-serine concentrations immediately after birth, both absolutely and relative to glycine and L-serine, declining to low values at infancy. D-Serine concentrations were almost undetectable in untreated 3-phosphoglycerate dehydrogenase-deficient patients. In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development.
