TY - JOUR
T1 - Primary cerebral and cerebellar astrocytes display differential sensitivity to extracellular sodium with significant effects on apoptosis
AU - Takeda, Tomohiko
AU - Makinodan, Manabu
AU - Fukami, Shin ichi
AU - Toritsuka, Michihiro
AU - Ikawa, Daisuke
AU - Yamashita, Yasunori
AU - Kishimoto, Toshifumi
PY - 2014/6
Y1 - 2014/6
N2 - 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+-Ca2+ 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.
AB - 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+-Ca2+ 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.
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U2 - 10.1002/cbf.3030
DO - 10.1002/cbf.3030
M3 - Article
C2 - 24888443
AN - SCOPUS:84901750964
SN - 0263-6484
VL - 32
SP - 395
EP - 400
JO - Cell Biochemistry and Function
JF - Cell Biochemistry and Function
IS - 4
ER -