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The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia

Isom, Amanda M
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
An estimated 35 million diabetic patients worldwide take antipsychotic medications for a variety of co-morbid mental illnesses. Diabetic patients frequently experience hypoglycemic episodes ranging from mild to severe. Interestingly, the combination of antipsychotic medications and hypoglycemia has remained largely unstudied. Both antipsychotic medications and hypoglycemia modulate extracellular glutamate creating the potential for glutamate-mediated excitotoxicity. The typical antipsychotic medication, haloperidol, has been shown to elevate extracellular glutamate levels through its binding pharmacology at the D2 and 5HT1A receptors. Conversely, quetiapine, an atypical antipsychotic medication, is not predicted to elevate extracellular glutamate through its binding pharmacology at the D2, 5HT1A, and 5HT2A receptors and may be less likely to induce this toxicity when combined with hypoglycemia. We hypothesized that haloperidol and hypoglycemia, not quetiapine and hypoglycemia, would elevate neuronal death and microglial activation. We predicted that this would occur through glutamate-mediated excitotoxicity potentiated by activated microglia. We investigated this hypothesis by combining these medications with a range of different hypoglycemic episodes: acute, severe; single, moderate; and multiple, moderate. The combination of severe hypoglycemia with these antipsychotic medications showed that both medications elevated neuronal death as compared to hypoglycemia alone. This suggests that the predicted abilities of quetiapine to attenuate extracellular glutamate levels and prevent glutamate-mediated excitotoxicity of neurons are overshadowed in instances of severe hypoglycemia. However, when moderate hypoglycemic episodes were combined with antipsychotic medications, no changes in neuronal death or microglial activation were detected. Overall, these data suggest that severe hypoglycemia and antipsychotic medications induce neuronal death, but the effects of these medications and moderate hypoglycemia on microglial activation may be more subtle in nature. These studies are relevant to the treatment and safety of the millions of diabetic patients taking antipsychotic medications who may be at risk for serious side effects.
Gary Gudelsky, Ph.D. (Committee Chair)
Steve Danzer, Ph.D. (Committee Member)
Andreas Loepke, M.D.Ph.D. (Committee Member)
Neil Richtand, M.D. (Committee Member)
Renu Sah, Ph.D. (Committee Member)
116 p.
Neurology
excitotoxicity; microglia; antipsychotic; haloperidol; quetiapine; cell death

Recommended Citations

Citations

  • Isom, A. M. (2014). The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111

    APA Style (7th edition)

  • Isom, Amanda. The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111.

    MLA Style (8th edition)

  • Isom, Amanda. "The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111

    Chicago Manual of Style (17th edition)

ucin1407407111
556
© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.