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Scholars Day: April 15, 2009

Impact of Hypoxia on Axonal Outgrowth in Mouse Cortical Neurons

Axonal plasticity is the ability of the axon to grow and change during development and in response to environmental demands. One environmental demand that influences axonal outgrowth is the hypoxic response. Hypoxia (<20% O2) affects cellular processes in physiological and pathological conditions. Hypoxia and the hypoxia mimetics Cobalt (II) Chloride and Deferoxamine (DFO) induce neurite outgrowth in cerebellar neurons and in PC12 cells. However, this has not been examined in cortical neurons, which show great plasticity in vivo following hypoxia/ischemia injury. Thus, our motivation was to quantify the effect of hypoxia and hypoxia mimetics on axonal outgrowth in cortical neurons. Mouse primary cortical neuronal cultures were treated with hypoxia or mimetics for 3 days. Individual neurons were imaged and axon lengths measured. Contrary to previous studies, neither hypoxia, DFO, nor CoCl2 significantly influenced the length of the axon. It is possible that mitochondria influence axonal plasticity and outgrowth but the role of mitochondrial movement on axonal growth has not been examined. We recently identified a mitochondrial-localized protein, HUMMR, which increases mitochondrial movement in acute (24 hour) hypoxia, but not in normoxia. HUMMR expression is highly up-regulated during hypoxia in a manner dependent on master transcription factor Hypoxia Inducible Factor-1 (HIF-1) neuronal cultures. shRNA knockdown of HUMMR increases mitochondrial movement in acute hypoxia but not in normoxia . HUMMR expression was inhibited using shRNA in primary neuronal cultures grown in hypoxia or normoxia for 4 days. Results showed no significant influence of HUMMR on axon length during chronic hypoxia. Future experiments will examine the influence of HUMMR under acute hypoxia.

Presenter: Jacqueline Tibbett (Undergraduate Student)
Topic: Biological Sciences
Location: 101 Edwards
Time: 1:15 pm (Session III)