The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia

The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia

Bibliographic Details
Main Author: Isom, Amanda M.
Language:English
Published: University of Cincinnati / OhioLINK 2014
Subjects:
Neurology
excitotoxicity
microglia
antipsychotic
haloperidol
quetiapine
cell death
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14074071112021-08-03T06:26:57Z The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia Isom, Amanda M. Neurology excitotoxicity microglia antipsychotic haloperidol quetiapine cell death 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. 2014-09-12 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Neurology
excitotoxicity
microglia
antipsychotic
haloperidol
quetiapine
cell death
spellingShingle Neurology
excitotoxicity
microglia
antipsychotic
haloperidol
quetiapine
cell death
Isom, Amanda M.
The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
author Isom, Amanda M.
author_facet Isom, Amanda M.
author_sort Isom, Amanda M.
title The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
title_short The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
title_full The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
title_fullStr The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
title_full_unstemmed The Cellular Consequences of Combining Antipsychotic Medications and Hypoglycemia
title_sort cellular consequences of combining antipsychotic medications and hypoglycemia
publisher University of Cincinnati / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1407407111
work_keys_str_mv AT isomamandam thecellularconsequencesofcombiningantipsychoticmedicationsandhypoglycemia
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