title: Dysregulated glutamate uptake by astrocytes causes oligodendroglia death in hypoxic perventricular white matter damage.
abstract: Excess glutamate mediates damage to oligodendroglia, resulting in myelination disturbances characteristic of hypoxic periventricular white matter (PWM) damage. We sought to examine if hypoxia altered the expression of astroglial excitatory amino acid transporters (EAAT1, EAAT2 and EAAT3) in the PWM, and, if so, whether it activated astroglial N-methyl D-aspartate receptors (NMDAR) which might lead to apoptosis of oligodendroglia. EAAT expression in the PWM of neonatal rats was measured at different time points after hypoxic exposure; it was attenuated at 7 and 14 d following hypoxia. Hypoxia prevented the uptake of glutamate by astroglial EAATs causing increased levels of extracellular glutamate. Excess glutamate augmented the expression of functional astroglial NMDAR. Following hypoxia, an increase in gap junction proteins between astroglia and oligodendroglia aided in the spreading of NMDAR-mediated excitotoxic calcium signals into the latter cell type triggering its apoptosis. Hence, dysregulated glutamate homeostasis is believed to contribute to hypoxia-induced death of oligodendroglia leading to neonatal PWM damage.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Madhuvika
authors.initials: M
authors.lastname: Murugan
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Charanjit
authors.initials: C
authors.lastname: Kaur
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism
chemical_list: D017630:Connexins; D050491:Glutamate Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: Astrocytes; Developing brain; Glutamate transporters; NMDAR receptors; Oligodendrocytes