Poster abstracts

Poster number 78 submitted by Swati Naphade

Progranulin is upregulated in response to contusion spinal cord injury

Swati Naphade (Molecular, Cellular and Developmental Biology, OSU), Kristina Kigerl (Center for Brain and Spinal Cord Repair and Dept. of Molecular Virology, Immunology & Medical Genetics, OSU), Sandra Kostyk (Center for Brain and Spinal Cord Repair and Dept. of Neuroscince, OSU), Lyn Jakeman (Center for Brain and Spinal Cord Repair and Dept. of Physiology and Cell Biology, OSU), Phillip Popovich (Center for Brain and Spinal Cord Repair and Dept. of Molecular Virology, Immunology & Medical Genetics, OSU), Jeff Kuret (Center for Molecular Neurobiology, OSU)

Abstract:
Progranulin (PGRN) is a pleiotrophic growth factor associated with neuroinflammation. It is implicated in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease and frontotemporal dementia, and is the only known growth factor to cause a neurodegenerative phenotype in humans through haploinsufficiency. Because of these correlations, we propose that PGRN expression is modulated in response to pathological insults associated with neuroinflammation. To test this hypothesis, PGRN expression was investigated in C57BL/6 mice subjected to mid-thoracic (T9 level) contusion spinal cord injury (which induces an acute and fulminant inflammatory response). Immunohistochemical staining of spinal cord sections obtained from non-injured laminectomy control animals revealed very low basal levels of PGRN expression throughout the grey matter. In contrast, sections prepared from injured animals revealed large increases in PGRN immunoreactivity throughout the injury epicenter that peaked 7-14 days post injury. Immunoblot analysis confirmed that increases in PGRN immunostaining after injury reflected PGRN protein levels. In injured animals, PGRN immunoreactivity colocalized with CD11b and CD68, indicating that the cellular sources of PGRN expression were activated microglia and macrophages. Microarray and RT-PCR analysis performed on RNA prepared from spinal cord homogenates revealed that increases in PGRN expression correlated with ~10 fold upregulation of PGRN mRNA. These data demonstrate that PGRN expression is dramatically induced at both the protein and mRNA levels following contusion SCI, and is positioned both spatially and temporally to influence recovery after SCI.

Keywords: progranulin, spinal cord injury