Abnormal calcium homeostasis in astrocytes from the trisomy 16 mouse

✍ Scribed by Linda L. Bambrick; Vera A. Golovina; Mordecai P. Blaustein; Paul J. Yarowsky; Bruce K. Krueger

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 842 KB
• Volume: 19
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199704)19:4<352::aid-glia8>3.0.co;2-z

✦ Synopsis

The regulation of intracellular Ca 2ϩ 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 2ϩ concentration ([Ca 2ϩ ] cyt ) was determined using digital imaging of fura-2-loaded cells. The relative Ca 2ϩ content of internal endoplasmic reticulum (ER) stores was estimated from the magnitude of the transient increase in [Ca 2ϩ ] cyt induced by cyclopiazonic acid (CPA), an inhibitor of Ca 2ϩ sequestration into ER stores. At rest, the average [Ca 2ϩ ] cyt was 140 nM in euploid (normal) astrocytes, but over twice as high, 320 nM, in Ts16 cells. In the absence of extracellular Ca 2ϩ , CPA induced a transient increase in [Ca 2ϩ ] cyt to over 1200 nM in Ts16 astrocytes as compared to only 500 nM in euploid cells, indicating an increased amount of Ca 2ϩ in the Ts16 astrocyte ER. In contrast to euploid astrocytes, both resting [Ca 2ϩ ] cyt and the amount of Ca 2ϩ in the ER stores varied widely among individual Ts16 astrocytes. These results show that Ts16 produces a dysregulation of Ca 2ϩ homeostasis leading to increased cytoplasmic and stored Ca 2ϩ . Since increases in [Ca 2ϩ ] cyt have been implicated in the etiology of neurodegenerative diseases, including AD, this finding of abnormal Ca 2ϩ homeostasis in a genetic model of human neurological disorders suggests that Ca 2ϩ dysregulation may be a common feature underlying neurodegenerative processes.