Graduation Year

2021

Document Type

Open Access Senior Thesis

Degree Name

Bachelor of Arts

Department

W.M. Keck Science Department

Second Department

Biology

Reader 1

Erin Jones

Reader 2

Alicia Bonaparte

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© 2021 Angel Sherpa

Abstract

Deficiency of Reelin, an extracellular glycoprotein, and overactivity of GSK3, a kinase downstream of Reelin, in the brain have been associated with bipolar disorder (BD). Overexpression of Reelin inhibits GSK3 activity by phosphorylation. However, it is unclear if the inhibition of GSK3 in the forebrain is a crucial element of Reelin signaling modulating bipolar-like behaviors. To fill this gap in our understanding, my first experiment proposes to examine if Reelin-deficient mice with reduced activity of GSK3 exhibit BD-like behaviors. If inhibition of GSK3 is indeed a crucial element of Reelin signaling modulating BD-like behaviors, then Reelin-deficient mice with decreased activity of GSK3 would not exhibit bipolar-like behaviors during behavioral assessments. Additionally, lithium—the first line treatment for BD—inhibits GSK3 activity both directly and indirectly, but those mechanisms are only partially known. Therefore, my second experiment proposes to examine the effects of varying concentrations of lithium on the mRNA and protein expression of Reelin to assess whether one of the ways by which lithium inhibits GSK3 activity is by increasing Reelin level. Increased Reelin level in response to lithium administration would suggest that one of the indirect ways by which lithium inhibits GSK3 activity and produces its therapeutic effects in bipolar patients is by increasing Reelin level in the brain as overexpression of Reelin inhibits GSK3 activity. The overall purpose of my proposed experiments is to separate and define the roles of GSK3 and Reelin in modulating behavioral phenotypes associated with BD.

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