Year of Publication
Master of Science (MS)
Arts and Sciences
Dr. Mark Prendergast
Excitotoxicity can lead to increases in intracellular Na+ and Ca2+ concentrations via the glutamatergic NMDA receptors, which can lead to cell death. Detailing the time-dependent degradation of neuronal components in response to excitotoxic challenge may help elucidate the sequence in which these signaling pathways are initiated and further, associate these pathways with topographic cellular demise. Using organotypic hippocampal slice culture technique, tissue from neonatal rat pups was exposed to NMDA, APV, or co-exposed for 24, 72 or 120 hours. Fluorescent microscopy of propidium iodide (PI) was used to evaluate neuronal membrane damage, changes in the density of mature soma (NeuN) and NMDA NR2B subunits were measured using immunohistochemical procedures. After 24 hours of exposure, the CA1 showed an increased PI signal and a decrease in NeuN marker, indicating somatic injury occurs shortly after excitotoxic challenge; these effects were blocked by co-administration of APV. Also in the CA1, loss of NR2B subunits, heavily expressed in dendritic processes, declined following 72 hours of exposure. Because somatic injury precedes loss of distal NR2B subunits, it is possible that these events involve different mechanisms, findings that may be relevant in the development of therapies to target neurodegeneration resulting from excitotoxicity.
Sharrett-Field, Lynda, "SOMATIC INJURY PRECEDES DISTAL ATROPHY FOLLOWING EXCITOTOXIC HIPPOCAMPAL INSULT" (2010). University of Kentucky Master's Theses. 70.