In Vivo Functional Imaging Reveals Impaired Neuronal and Astrocytic Calcium Regulation in Alzheimer's Disease
Author | : Kishore V. G. S. Kuchibhotla |
Publisher | : |
Total Pages | : 390 |
Release | : 2009 |
ISBN-10 | : OCLC:961834208 |
ISBN-13 | : |
Rating | : 4/5 (08 Downloads) |
Book excerpt: I next posited that plaque deposition might also impact the function of astrocyte networks. Using multiphoton fluorescence lifetime imaging microscopy in vivo, I quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time lapse imaging revealed that calcium transients in astrocytes were more frequent, were synchronously coordinated across long distances, and were uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-13 plaques, originating near plaques and spreading radially at least 200 [mu]m. Thus, while neurotoxicity is observed near amyloid-B deposits, there exists a more general astrocyte-based network response to focal pathology. Taken together, it appears that plaque deposition does not lead to the deterministic degeneration, or dysfunction, of all cells in the cortical network: certain dendrites are vulnerable to calcium overload whereas others are less so. Moreover, A[beta] appears to globally impact astrocytes whereas plaques locally impair neuronal function. This complex and multidimensional impact of A[beta] argues that a novel, combinatorial approach to therapeutic intervention might prove effective.