| Alzheimer's Disease (AD) is the most devastating age-related neurodegenerative disease affecting more than 26 million people worldwide in 2006, whose neuropathological hallmarks include loss of neurons, deposition of neuritic plaques, and neurofibrillary tangles in brain regions. Amyloid-beta-peptide (Abeta) and calcium dysregulation are suggested to be the possible causes for AD, while little evidence has shown the coupled effects of the two on astrocytes, especially in terms of reactive astrocytosis which is one of distinct features in AD. In the endeavor to scrutinize the associated effects of Alzheimer's Abeta and disrupted calcium homeostasis on reactive astrogliosis, we explored how Abeta act on reactive astrocytes modulated by [Ca2+] i, which was illustrated by the protein expression of two reactive gliosis markers, S100B and GFAP. The effect of Abeta on intracellular calcium oscillations in astrocytes was also studied. Quantification of protein expression level with time revealed that the expression of S100B induced by Abeta was calcium-dependent. GFAP expression level in Abeta condition was also modulated by [Ca 2+]i and in addition possibly by S100B in a concentration-dependent manner. In the calcium experiment, Abeta was found to increase intracellular calcium oscillations in astrocytes, while this augmentation in oscillations could be suppressed by thapsigargin and BAPTA-AM. More importantly, spontaneous intercellular calcium waves were first observed in and only in Abeta condition, in which the wave was presented in two forms, radial and unidirectional. The response to calcium modulation in Abeta model was suggested to be a type of astrocytic accommodations in AD. |
