Eugene Kim (Tamara Kinzer-Ursem, advisor), “The Role of CaMKII, Drebrin-A, and F-actin Tripartite in Homeostatic Plasticity”

Abstract: Homeostatic plasticity is defined as the neuron’s ability to stabilize its activity to a particular set point, such as the average neuronal firing rate. There is much-emerging evidence that suggests disrupted homeostatic synaptic plasticity leads to neuropsychiatric and neurologic disorders, such as autism spectrum disorder (ASD), Fragile X Syndrome (FXS), and Alzheimer’s disease (AD). Out of many ways to regulate homeostatic plasticity, structure-based homeostatic plasticity is one of them. However, structural homeostatic plasticity at the spine head is mainly studied at the post-synaptic density (PSD) and shows wide variance across all studies, such as in-vitro and brain slices. Specifically, spine head enlargement is commonly seen through Ca2+/calmodulin-dependent protein kinase (CaMKII) and filamentous actin (F-actin), but understanding how this translates into structural homeostatic plasticity is lacking. Recent studies have shed light upon the role of Drebrin-A, an actin-binding protein that forms stable F-actin meshes in dendritic spines, and its binding properties with CaMKII and F-actin. However, no studies have shown the interaction of CaMKII, Drebrin-A, and F-actin as a tripartite and how it influences structural homeostatic plasticity. We propose to define the localization of the tripartite in dendritic spine heads and characterize structural homeostatic plasticity due to the tripartite and its interaction with other cytoskeletal proteins using super-resolution microscopy (SRM). Contrary to PSD F-actin dynamics, this tripartite localized at the head-neck interface may serve as a critical indicator in structured-based homeostatic plasticity. Understanding the relationship between tripartite and homeostatic plasticity will open new avenues of pharmacological targets in neuropsychiatric and neurologic disorders.

Evaluation link Eugene Kim: https://purdue.ca1.qualtrics.com/jfe/form/SV_6msN1LlhsrNzY9g

Rachel Stingel (Riyi Shi, advisor), Excitotoxicity and acrolein damage following (or caused by) spinal cord injury - the role of GLT-1

Abstract: Spinal cord injury (SCI) is a devastating condition that causes variable and often significant sensory, motor, and autonomic dysfunction. Despite extensive research, the limited efficacy of clinical treatments highlights the need for a better understanding of the complex pathology underlying SCI in order to identify new treatment strategies for functional restoration. Immediately following the initial injury (primary injury), secondary inflammatory cascades (secondary injury) perpetuate the extent of damage, and worsen functional outcomes. Acrolein is a reactive α,β-unsaturated aldehyde that forms within hours and remains active for at least two weeks following SCI. It has been found to play an instrumental role in SCI-induced neurodegenerative mechanisms such as oxidative stress, mitochondrial dysfunction, and lipid peroxidation. Excitotoxicity resulting from excess extracellular glutamate accumulation is also heavily implicated in cell death following SCI as well as other neurodegenerative disorders. Synaptic glutamate levels are primarily regulated by glutamate transporter-1 (GLT-1) on astrocyte cell membranes. Evidence showing GLT-1 function is compromised by less reactive aldehydes suggests its potential as a key target for acrolein-mediated dysfunction that could lead to excitotoxicity and neurodegeneration. Thus, we sought to robustly characterize GLT-1 expression following acute SCI and determine if acrolein mediates these findings. Using a clinically relevant T10 contusion model of SCI, we show that: 1) GLT-1 and acrolein levels display an inverse expression pattern as revealed by immunoblotting and immunohistochemical labeling, 2) GLT-1 and acrolein co-localize and co-precipitate following SCI, and 3) the application of exogenous acrolein to intact spinal cord tissue sufficiently reduces GLT-1 expression. Together, these findings have important implications for understanding potential acrolein-mediated excitotoxicity, neuronal regions most at risk, and may reveal targets for therapeutic intervention following acute SCI.

Evaluation link Rachel Stingel: https://purdue.ca1.qualtrics.com/jfe/form/SV_0udG1PftA4ygOR8

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https://purdue-edu.zoom.us/j/98231659969?pwd=T21Oa1B6QzFyQzFvckMzS1doNGlJUT09

Meeting ID: 982 3165 9969, Passcode: biomedical