Date of Graduation
12-2009
Document Type
Dissertation (PhD)
Program Affiliation
Biomedical Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Cheng Chi Lee
Committee Member
Michael Blackburn
Committee Member
William Dubinsky
Committee Member
Henry Strobel
Committee Member
Rodney Kellems
Abstract
Our laboratory’s ability to induce deep hypometabolism (DH) via an injection of adenosine monophosphate (5’-AMP) followed by placement in an ambient temperature (Ta) around 15oC currently can last about 3-9 hours. While we have insight into how 5’-AMP induced hypometabolism is initiated, it remains unclear how arousal from hypometabolism is controlled. Other laboratory members have been unable to prolong this process safely and effectively with previous attempts of re-injecting a dose of 5’-AMP upon arousal or by decreasing the Ta. While these methods worked in suppressing arousal, the mortality rate is also increased. To gather a better understanding of the process, a metabolic panel from serum samples was run giving insight into possible biochemical events occurring from euthermia to DH to spontaneous arousal and back to euthermia. Analyzing this data revealed many changes in metabolites. A few metabolites that stood out such as glucose and pyruvate did not alter the outcome in arousal rate over saline injection. Additional metabolite analysis revealed that an amino acid, arginine, was significantly reduced during DH. This amino acid seems to be a key component in prolonging our process possibly due to its intricate role in the urea cycle. Supplemental arginine is clearly more beneficial both in suppressing arousal and increasing the survival rate after 12 hours in DH.
Keywords
hypometabolism, 5’-AMP, Suspended Animation, urea cycle, Metabolomics, energy utilization, hibernation, purine metabolism, mouse, hypothermia