IMPAIRED CA-SIGNALING IN ASTROCYTES FROM THE TS16 MOUSE MODEL OF DOWN-SYNDROME

The trisomy 16 mouse model of Down syndrome has been used to compare c alcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic m ice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM l oaded primary astroglial cultures prepared from the hippocampus shows that resting Ca levels are on average significantly higher in trisomic than in the control astrocytes (280 vs. 120 nM). Serotonin (3 mu M) a nd glutamate (30-300 mu M) evoked transient Ca-increases from 400 to 6 00 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Im aging of ATP-driven Ca-accumulation in cellular organelles revealed a significantly stronger uptake of Ca in trisomic astrocytes that might buffer cytosolic Ca-increases. Our results demonstrate major disturban ces in Ca-signaling in trisomic astrocytes that are likely to be of pa thophysiological relevance. (C) 1997 Elsevier Science Ireland Ltd.