Premium
Abnormal calcium homeostasis in astrocytes from the trisomy 16 mouse
Author(s) -
Bambrick Linda L.,
Golovina Vera A.,
Blaustein Mordecai P.,
Yarowsky Paul J.,
Krueger Bruce K.
Publication year - 1997
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199704)19:4<352::aid-glia8>3.0.co;2-z
Subject(s) - cyclopiazonic acid , homeostasis , astrocyte , biology , extracellular , endoplasmic reticulum , calcium metabolism , intracellular , microbiology and biotechnology , cytoplasm , neurodegeneration , calcium , medicine , endocrinology , central nervous system , disease
The regulation of intracellular Ca 2+ was investigated in cultured astrocytes from the trisomy 16 (Ts16) mouse, an animal model for Down syndrome and Alzheimer's disease (AD). The cytoplasmic ionized Ca 2+ concentration ([Ca 2+ ] cyt ) was determined using digital imaging of fura‐2‐loaded cells. The relative Ca 2+ content of internal endoplasmic reticulum (ER) stores was estimated from the magnitude of the transient increase in [Ca 2+ ] cyt induced by cyclopiazonic acid (CPA), an inhibitor of Ca 2+ sequestration into ER stores. At rest, the average [Ca 2+ ] cyt was 140 nM in euploid (normal) astrocytes, but over twice as high, 320 nM, in Ts16 cells. In the absence of extracellular Ca 2+ , CPA induced a transient increase in [Ca 2+ ] cyt to over 1200 nM in Ts16 astrocytes as compared to only 500 nM in euploid cells, indicating an increased amount of Ca 2+ in the Ts16 astrocyte ER. In contrast to euploid astrocytes, both resting [Ca 2+ ] cyt and the amount of Ca 2+ in the ER stores varied widely among individual Ts16 astrocytes. These results show that Ts16 produces a dysregulation of Ca 2+ homeostasis leading to increased cytoplasmic and stored Ca 2+ . Since increases in [Ca 2+ ] cyt have been implicated in the etiology of neurodegenerative diseases, including AD, this finding of abnormal Ca 2+ homeostasis in a genetic model of human neurological disorders suggests that Ca 2+ dysregulation may be a common feature underlying neurodegenerative processes. GLIA 19:352–368, 1997. © 1997 Wiley‐Liss, Inc.