Project description:To investigate the determinants of neuronal survival after traumatic brain injury, we compared the transcriptional profiles of dying (Fluoro-Jade-positive) and immediately adjacent surviving (Fluoro-Jade-negative) neurons from the CA3 subfield of the rat hippocampus 24 hours after experimental TBI. We found that hippocampal neurons that survive TBI invariably express high levels of genes that have cellular functions involved in survival, regeneration, development, proliferation, neuronal plasticity such as cAMP response element binding protein (CREB), brain-derived-neurotrophic factor (BDNF) and mitogen-activated protein kinase 1 (MAPK1). Dying neurons express high levels of genes involved in aberrant cell cycle progression, immune response, inflammation, oxidative stress and apoptosis such as Interleukin-1β (IL-1β), caspase 3 and B-cell linker (BLNK). We conclude that shifting the balance between the global levels of these proteins with pharmacotherapeutic drugs that induce expression of cell survival associated genes, is expected to alter the cellular rheostat that determines cell survival or cell death. Replicate pooled samples (approximately 600 laser capture microdissected hippocampal neurons per sample of dying neurons (labeled with Fluoro-Jade, a fluorescent stain for degenerating CNS neurons) and surviving neurons (Fluoro-Jade-negative) were hybridized in duplicate to rat Agilent whole genome arrays.
Project description:To investigate the determinants of neuronal survival after traumatic brain injury, we compared the transcriptional profiles of dying (Fluoro-Jade-positive) and immediately adjacent surviving (Fluoro-Jade-negative) neurons from the CA3 subfield of the rat hippocampus 24 hours after experimental TBI. We found that hippocampal neurons that survive TBI invariably express high levels of genes that have cellular functions involved in survival, regeneration, development, proliferation, neuronal plasticity such as cAMP response element binding protein (CREB), brain-derived-neurotrophic factor (BDNF) and mitogen-activated protein kinase 1 (MAPK1). Dying neurons express high levels of genes involved in aberrant cell cycle progression, immune response, inflammation, oxidative stress and apoptosis such as Interleukin-1β (IL-1β), caspase 3 and B-cell linker (BLNK). We conclude that shifting the balance between the global levels of these proteins with pharmacotherapeutic drugs that induce expression of cell survival associated genes, is expected to alter the cellular rheostat that determines cell survival or cell death.
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.