Down-regulated GFAPα: a major player in heavy metal induced astrocyte damage

Exposure to a mixture of As, Pb and Cd induces apoptosis and morphological alterations in the cortical astrocytes of rat brain. The levels of the glial fibrillary acidic protein (GFAP) undergo a reduction. The GFAP exists in several isoforms, viz., α, β, κ, δ and ϵ. However, contribution of the isoforms towards astrocyte damage is not understood. We investigated the effect of the metal mixture (MM) on the expression profiles of mRNAs encoding the GFAP isoforms in astrocytes. The MM was administered in drinking water to developing rats till postnatal day (PD) 60. We observed a fall (10.20 ± 1.04%, 18.91 ± 2.12% and 30.26 ± 3.21% at PD24, PD45 and PD60 respectively) in GFAPα. This may have been compensated by a rise in β, κ, and ϵ. The GFAPδ remained unchanged. To determine the role of the GFAPα, we silenced its gene using SiRNA technology in the rat primary astrocytes. We observed a 23.73 ± 1.56% increase in the number of apoptotic cells. The cleaved PARP and Bax levels increased by 2.48 ± 0.14-fold and 3....