Abstract
Astrocytes are one of the most important non-neuronal cell types of the nervous system, which are playing an essential role in physiology and diseased states of the brain. However, many facets of the astrocytes are still unknown, making it difficult to deduce an exact mechanism behind their involvement in physiological functions,
such as normal aging and neurodegeneration. This lack of complete understanding of astrocytes highlights the requirement for better and more efficient data and tools to delineate biological roles of these cells. The development of such technologies will increase the understanding of astrocytes and will also help in paving the path for both in-vivo and in-vitro manipulation of astrocytes and their specific molecules. The methodology development can open up a new dimension for therapeutic interventions. It is only recently that the attention has been shifted towards the potential role of astrocytes in pathogenesis like neurodegeneration, something that
has always been associated with neurons in the past.
Various studies are now focused on analyzing the role of astrocytes in aging and neurodegeneration; however, such analysis require efficient tools that can increase the accuracy of cell targeting. Thus, the first aim of this study was to analyze cell type specificity of two astrocyte promoters, the GFAP and the GfaABC₁D promoters,
by targeting astrocytes via recombinant adeno associated virus (rAAV) vectors and comparing the off-target neurons. The second aim was to explore the brain astrocytes during aging and in neurodegenerative disorders by quantifying and comparing the
densities of astrocytes in the mouse cortex and hippocampus in early-aged (3-5-month-old) and old-aged (>18 month-old) wild-type mice, as well as in an AD mouse model, the APP/PS1 mice.
Upon analysis, it showed that the transduction capacity and cell type specificity of both promoters were comparable and dependent upon brain regions. Furthermore, it was found that age and neurodegeneration do affect the density of astrocytes, although the effect of age was not prominent.
