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 calcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic mice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM loaded 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 microM) and glutamate (30-300 microM) evoked transient Ca-increases from 400 to 600 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Imaging 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 disturbances in Ca-signaling in trisomic astrocytes that are likely to be of pathophysiological relevance.
Müller
W
W
Institut für Physiologie der Charité, Humboldt Universität zu Berlin, Germany.
Heinemann
U
U
Schuchmann
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D014314:Trisomy
D005456:Fluorescent Dyes; C049925:fura-2-am; D012701:Serotonin; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2