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Publication Date

2025-5

First Advisor

Sharon Owino

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Neuroscience

Keywords

GPR37, Wnt pathway, stroke, LRP6, cell culture

Abstract

Stroke is a debilitating medical condition affecting thousands of people in the United States each year. Ischemic stroke, which accounts for 80% for all cases, occurs when a blood clot blocks a cerebral blood vessel. This blockage restricts the flow of oxygen, glucose, and essential nutrients to the brain, leading to cell death and potentially permanent brain damage. Currently, the only FDA-approved treatment for ischemic stroke is tissue plasminogen activator (tPA), which must be administered within a narrow time to be effective. Due to this limitation, researchers have been actively exploring alternate, more accessible treatment options. One promising approach involves an injection of self-derived neural progenitor cells into the brain. These cells have the potential to differentiate into neurons, thereby replenishing those that have been lost as a result of the stroke. This differentiation process is critically dependent on the canonical Wnt/ β-catenin signaling pathway, which plays a key role in neural development and regeneration. Additionally, GPR37 has been shown to potentiate the Wnt pathway. Therefore, the primary objective of this study was to characterize the role of GPR37 in the Wnt pathway to enhance the efficiency and success rate of a novel stroke therapeutic. Using in vitro approaches, results indicate that under baseline conditions, GPR37 reduces LRP6 levels and suppresses Wnt signaling. Further experiments demonstrated a direct interaction between GPR37 and LRP6. When these findings were translated into an in vivo model, GPR37 did not appear to influence Wnt signaling in the hippocampus and the cortex. However, GPR37 may impact neuronal maturation specifically in the cortex, potentially through a Wnt-independent mechanism. Finally, additional experiments revealed that GPR37 may also influence cell growth, immune function, and cellular morphology.

Rights

©2025 Anika Raghavan. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

Comments

78 pages: color illustrations. Includes bibliographical references (pages 69-78).

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