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Characterization of a novel animal model of bipolar disorder

Project Full Title:

Do elevated plasma homocysteine levels during neonatal and postnatal development contribute to depressive and manic behaviors typically associated with bipolar disorder?

Project Mentor(s):

Brown,Kenneth; Chase,Leah

Project Mentor(s) EMail:

brownk@hope.edu; chase@hope.edu

Project Start Date:

5/13/2020

Project End Date:

7/19/2020

Project Description:

This interdisciplinary project will incorporate the disciplines of biology, chemistry and neuroscience. The project is specifically housed within the Hope College Departments of Biololgy and Chemistry. Therefore, interested students can elect to participate in either summer research program.

Bipolar disorder is a serious mood disorder that is characterized by periods of depression and mania. The development of novel therapies for this disorder has been hampered by the lack of a reliable animal model. We recently discovered that treatment of rats from postnatal day 3-18 with the glutamatergic agonist, homocysteic acid (HCA), leads to the development of manic and depressive behaviors in male and female rats. This model was developed based upon the clinical observation that elevated levels of the amino acid, homocysteine (HCY), are associated with the development of neuropsychiatric disorders. However, we reasoned that HCA, which is the oxidized metabolite of HCY, may actually dysregulate important glutamatergic pathways in the brain resulting in behaviors consistent with the bipolar phenotype. In order to provide strong construct validity to our new animal mode, we plan to directly test the hypothesis that elevated levels of HCY during the same critical period in developing rats will lead to an increase in HCA levels in the plasma and brain and the development of a mixed depressive/manic state. The specific goal for this summer is to complete the measurement of HCA and HCY levels in the plasma and brains rats exposed to high HCY during development. These data will analyzed in combination with our previous behavioral assessment of HCY treated rats so that we can better understand the link between HCA levels and the development of manic and depressive behaviors.

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