title: Primary cerebral and cerebellar astrocytes display differential sensitivity to extracellular sodium with significant effects on apoptosis.
abstract: Central pontine myelinolysis is one of the idiopathic or iatrogenic brain dysfunction, and the most common cause is excessively rapid correction of chronic hyponatraemia. While myelin disruption is the main pathology, as the diagnostic name indicates, a previous study has reported that astrocyte death precedes the destruction of the myelin sheath after the rapid correction of chronic low Na(+) levels, and interestingly, certain brain regions (cerebral cortex, hippocampus, etc.) are specifically damaged but not cerebellum. Here, using primary astrocyte cultures derived from rat cerebral cortex and cerebellum, we examined how extracellular Na(+) alterations affect astrocyte death and whether the response is different between the two populations of astrocytes. Twice the amount of extracellular [Na(+) ] and voltage-gated Na(+) channel opening induced substantial apoptosis in both populations of astrocytes, while, in contrast, one half [Na(+) ] prevented apoptosis in cerebellar astrocytes, in which the Na(+) -Ca(2+) exchanger, NCX2, was highly expressed but not in cerebral astrocytes. Strikingly, the rapid correction of chronic one half [Na(+) ] exposure significantly increased apoptosis in cerebellar astrocytes but not in cerebral astrocytes. These results indicate that extracellular [Na(+) ] affects astrocyte apoptosis, and the response to alterations in [Na(+) ] is dependent on the brain region from which the astrocyte is derived.
authors.affiliation: Department of Psychiatry, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takeda
authors.forename: Manabu
authors.initials: M
authors.lastname: Makinodan
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Fukami
authors.forename: Michihiro
authors.initials: M
authors.lastname: Toritsuka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ikawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism*; D061251:Primary Cell Culture; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium
keywords: apoptosis; astrocyte; central pontine myelinolysis; hyponatraemia; schizophrenia; sodium ion