期刊
NEUROBIOLOGY OF AGING
卷 28, 期 1, 页码 99-111出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2005.11.004
关键词
Ca2+ waves; mitochondria; IP3; ATP; two-photon; nerve growth factor; PC12 cells
资金
- NIA NIH HHS [AG19316] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [P01AG019316] Funding Source: NIH RePORTER
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 (Delta psi) 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. Alps 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. (c) 2005 Elsevier Inc. All rights reserved.
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