Abstract P120: Down Regulation of Add3 in Astrocytes Induces Pro-inflammatory and Fibrotic Factors and May Contribute to Alzheimer’S-related Dementias [Session Title: Onsite Poster Competition I With Reception]

We genetically mapped a mutation in Add3 in FHH rats that decreases Add3 expression in various tissues, including brain and cerebral vessels, and further decreases with age in comparison with FHH.1BN congenic rats in which Chr. 1 from BN rats containing 15 genes, including Add3, was transferred onto FHH genetic background. More recently, we demonstrated that Add3 dysfunction contributes to cerebral vascular impairments in FHH rats, and they exhibit BBB leakage and neurodegeneration after the development of hypertension. In addition, Aβ protein expression in the brain in FHH rats is increased as early as 8 weeks of age. Reactive astrogliosis is a common finding in neurodegenerative diseases and activated astrocytes promote neurodegeneration. Moreover, astrocyte dysfunction affects Aβ clearance and Aβ accumulation is a well-defined feature of Alzheimer’s disease. To further explore whether astrocytes contribute to neurodegeneration and cognitive impairments in FHH rats, we knocked down Add3 expression using Add3 Dicer-substrate RNAi (DsiRNA) in human astrocytes and found that GFAP and IL-6 expression was markedly enhanced in comparison to scramble siRNA treated cells using a q-PCR array. Moreover, the expression of TGF-β2 and TGF-β3 was elevated by 2.0 ± 2.9 and 1.8 ± 1.8 folds, respectively, in Add3 DsiRNA treated astrocytes. In addition, the actin cytoskeleton was disrupted in Add3 DsiRNA treated astrocytes. We found that FHH rats exhibit a reduction in neuronal dens...
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Abstract Presentations Source Type: research