Thursday, May 2, 2024
5/2/2024
Project Summary The goal of the parent grant is to determine the role of oxidative stress in astrocytic glial fibrillary acidic protein (GFAP) upregulation. The supplemental research addresses a related but in depth mechanism to investigate the role of GFAP and a related protein, vimentin in seizure-induced astrogliosis. Mitochondrial dysfunction, oxidative stress and neuroinflammation are implicated as mediators of epilepsy and/or its comorbidities. The in depth mechanisms underlying seizure-induced astrogliosis, particularly the upregulation of GFAP remain at large. We have observed robust transcriptional upregulation of GFAP and vimentin in mice lacking the mitochondrial anti- oxidant manganese superoxide dismutase-2 (Sod2) in forebrain neurons. The goal of these studies is to utilize primary neuronal-glial cultures to determine the role of reactive cysteine residues in GFAP and vimentin as the triggers for astrogliosis. Aim 1 will test the ability of two redox cycling compounds for their ability to activate GFAP mRNA expression as a result of posttranslational redox modification of a conserved cysteines in GFAP and vimentin. Studies will determine if neuronal and specifically mitochondrial ROS is sufficient to induce GFAP upregulation and astrogliosis in vitro using mixed rat neuronal culture. Aim 2 will determine if upregulation of GFAP and vimentin protein expression in mixed neuronal cultures occurs due to redox modification. These studies could reveal mechanisms by which astrogliosis is initiated in neurological diseases such as epilepsy.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
