Related Experiment Video
Updated: Jul 16, 2026
Deriving the Time Course of Glutamate Clearance with a Deconvolution Analysis of Astrocytic Transporter Currents
Published on: August 7, 2013
The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter
Tara M Desilva1, Hannah C Kinney, Natalia S Borenstein
1Neurobiology Program, Children's Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Insights
Periventricular leukomalacia (PVL) in premature infants may stem from excitotoxicity to oligodendrocyte precursors. Transient expression of glutamate transporter EAAT2 in fetal white matter may contribute to this injury.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Periventricular leukomalacia (PVL) is a key brain abnormality in premature infants, affecting immature cerebral white matter.
- Oligodendrocyte precursors (pre-OLs) are abundant during the PVL vulnerability period (24-32 weeks gestation) and susceptible to excitotoxicity.
- Cerebral ischemia/reperfusion can lead to energy failure, reversing glutamate transport and causing excitotoxic damage to pre-OLs.
Purpose of the Study:
- To identify and localize glutamate transporters in human cerebral white matter during the period relevant to PVL.
- To investigate the developmental expression profile of glutamate transporters EAAT1, EAAT2, and EAAT3 in relation to PVL vulnerability.
Main Methods:
- In situ hybridization was used to analyze the mRNA expression of EAAT1, EAAT2, and EAAT3 in human fetal white matter.
- Immunoblotting assessed EAAT2 protein expression levels during early development.
- Double-label immunocytochemistry localized EAAT2 within specific cell types (oligodendrocytes, astrocytes, axons).
Main Results:
- EAAT2 mRNA was highly abundant in human fetal white matter during the peak PVL incidence period, decreasing significantly by 2 months postnatally.
- EAAT2 protein was highly expressed in early development compared to adult levels.
- EAAT2 was localized to oligodendrocytes (OLs) in fetal white matter, not astrocytes or axons.
Conclusions:
- The transient, developmentally regulated expression of EAAT2 in oligodendrocytes during the PVL vulnerability window suggests its significant role.
- EAAT2 may be a primary source of extracellular glutamate during ischemic injury in the preterm infant's cerebral white matter.
- This transporter's transient upregulation points to a potential mechanism contributing to PVL pathogenesis.
Abstract:
The major brain abnormality underlying cerebral palsy in premature infants is periventricular leukomalacia (PVL), a lesion of the immature cerebral white matter. Oligodendrocyte precursors (pre-OLs; O4(+)O1(-)) predominate in human cerebral white matter during the peak time frame for PVL (24-32 gestational weeks) and are vulnerable to excitotoxicity. We hypothesize that PVL reflects, in part, excitotoxicity to pre-OLs resulting from cerebral ischemia/reperfusion. Reversal of glutamate transport in the setting of energy failure is a major source of pathologic accumulation of extracellular glutamate. Here, we identify and localize the glutamate transporters in human cerebral white matter during the age range of PVL. In situ hybridization was performed with digoxigenin-labeled probes directed against the full-length coding regions of EAAT1, EAAT2, and EAAT3. EAAT2 mRNA was abundant in human fetal white matter during the period of peak incidence of PVL and virtually disappeared by 2 postnatal months. Its developmental profile differed significantly from that of both EAAT1 and EAAT3 mRNA. Immunoblotting demonstrated that EAAT2 protein was highly expressed in early development relative to adult values. Double-label immunocytochemistry detected EAAT2 in OLs but not astrocytes or axons in the human fetal white matter. We conclude that transient expression of EAAT2 occurs during the window of peak vulnerability for PVL, suggesting that this developmentally up-regulated transporter may be a major source of extracellular glutamate in ischemic injury to the cerebral white matter of the preterm infant.
