Ca2+ signaling, mitochondria and sensitivity to oxidative stress in aging astrocytes.
Age-related changes in astrocytes that could potentially affect neuroprotection have been largely unexplored. To test whether astrocyte function was diminished during the aging process, we examined cell growth, Ca2+ signaling, mitochondrial membrane potential (DeltaPsi) and neuroprotection of NGF-differentiated PC12 cells. We observed that cell growth was significantly slower for astrocytes cultured from old (26-29 months) mice as compared to young (4-6 months) mice. DeltaPsis in old astrocytes were also more depolarized (lower) than in young astrocytes and old astrocytes showed greater sensitivity to the oxidant tert-butyl hydrogen peroxide (t-BuOOH). ATP-induced Ca2+ responses in old astrocytes were consistently larger in amplitude and more frequently oscillatory than in young astrocytes, which may be attributable to lower mitochondrial Ca2+ sequestration. Finally, NGF-differentiated PC12 cells that were co-cultured with old astrocytes were significantly more sensitive to t-BuOOH treatment than co-cultures of NGF-differentiated PC12 cells with young astrocytes. Together, these data demonstrate that astrocyte physiology is significantly altered during the aging process and that the astrocyte's ability to protect neurons is compromised.
Lin
Da-Ting
DT
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, United States.
Wu
Jun
J
Holstein
Deborah
D
Upadhyay
Geeta
G
Rourk
Wendy
W
Muller
Elizabeth
E
Lechleiter
James D
JD
D000375:Aging / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*