Electronic Thesis and Dissertation Repository


Master of Science


Anatomy and Cell Biology


Dr. Marco Prado

2nd Supervisor

Dr. Vania Prado

Joint Supervisor


Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrPC) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrPC, α7nAChR, and ALK2 prior to oxygen-glucose deprivation (OGD). STI1 treatment significantly decreased apoptosis and cell death in neurons submitted to OGD in a manner dependent on PrPC, α7nAChR, and ALK2. Activation of both the α7nAChR and ALK2 receptor were effective at decreasing neuronal death in response to ischemia, suggesting that α7nAChR and ALK2 receptor may be novel targets for preventing death of neurons after ischemia.