Date of Award
Master of Science (MS)
One of the most complex and intriguing biological problems is perhaps the development of neurodegeneration. Neurodegenerative diseases are many, and many seem to be their causes: their etiologies are generally of different nature, making their study difficult and highlyspecialized. Lately, however, one process in particular, neuroinflammation, has surfaced as astrong common feature in a variety of neurodegenerative diseases (Alzheimer’s, Amyotrophic Lateral Sclerosis, Frontal Temporal Lobar Dementia, Multiple Sclerosis, Parkinson’s, Rett’s Syndrome, and more) suggesting that this is either a mechanism through which our brain responds to neural dysfunction or is directly responsible for the initiation of various pathologies of the nervous system. Nonetheless, its contribution to disease is still very unclear. In light of this, I and Dr. LaRocca set out to investigate the role of the innate immune response in an in vitro amyotrophic lateral sclerosis model: TDP-43 knockdown primary rat astrocytes. Here, I describe the activation of the intracellular innate immune response in such astrocytes upon the silencing of TDP-43. I used RNA-Seq data (generated and analyzed by Dr. LaRocca), immunofluorescence staining, and quantitative real time-PCR (qRT-PCR) to detect the differential expression of innate immune response markers, and fluorescence in-situ hybridization to investigate the expression and localization of repetitive elements. We have identified specific immune markers that are reliably overexpressed in our ALS model, increased expression of repetitive elements, and an increased accumulation of cytoplasmic dsRNA. These results pave the way for future in vivo studies on the role of dsRNA, repetitive elements, and inflammation in neurodegeneration.
Mariani, Andrea, "Amyotrophic Lateral Sclerosis: a Proposed Molecular Model of Disease" (2018). Integrative Physiology Graduate Theses & Dissertations. 87.