Date on Senior Honors Thesis

5-2026

Document Type

Senior Honors Thesis (Legacy)

Degree Name

B.S.

Department

Psychological and Brain Sciences

Committee Chair

David Stirling

Committee Member

Jeffrey Petruska

Committee Member

Thomas Reidel

Author's Keywords

spinal cord injury; microglia; STIM proteins; inflammation; store-operated calcium entry (SOCE); neuroscience

Abstract

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to understand the role of each of those STIM proteins in the spinal cord’s resident immune cell, microglia, by investigating the functional and histological outcomes after knocking out either microglial-specific STIM1 (mSTIM1), or mSTIM2. We ran Basso Mouse Scale (BMS) tests, horizontal ladder assessments, white matter sparing (WMS), and immunohistochemistry (IHC). We analyzed six-week longitudinal behavioral study and histology, in addition to a 2-week acute histological study. We found that there was significantly increased spared white matter at the 6- and 2-week mark, suggesting that mSTIM2 KO causes secondary white matter injury as early as 2 weeks. We also found improved behavioral outcomes, particularly at the 2-week time point in the 6-week behavior experiment. This work not only provides more insight to the inflammatory response that occurs post-SCI, but also provides additional understanding into microglial cellular interaction, neuroinflammation, and intracellular ion importance. This particularly highlights how microglial-STIM2 calcium signaling can exacerbate these secondary injury processes, and offers more information on potential targets for developing therapeutics to improve patient recovery after SCI.

Lay Summary

The bundle of nerves that connect your brain to your muscles that controls motor movement and sensory perception, is called your spinal cord. When your spinal cord is injured, it often results in individuals being unable to move their limbs, control bladder function, or feel anything, depending on where the injury was located on the spine. One of the primary ways that cells communicate with each other or activate is through an ion called calcium entering the cell. If calcium levels are too low, then there is a pathway that can detect the low stores and allow new calcium into the cell referred to as store-operated calcium entry. If the new calcium into the cell is overloaded, it can cause the immune cells of the spinal cord, microglia, to become too reactive, causing them to be harmful. This is a part of secondary injury after a spinal cord injury and is being studied to potentially aid in the development of future therapeutics for humans that have spinal cord injuries.

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