About me
Investigating Mitochondrial Damage in GABAergic Neurons and Spinal Cord Epigenetic Modifications Following Spinal Cord Injury-Induced Chronic Pain
Location: 65
Mentor: Dr. Stanislava Jergova
Spinal cord injury (SCI) results in chronic neuropathic pain with a lack of long-standing treatments. Gamma-Aminobutyric Acid (GABA) disinhibition and increased excitatory glutamate release are key factors to abnormal pain perception. Elevated levels of glutamate might cause GABAergic disinhibition and pain development by inducing mitochondrial damage that impairs cellular function. However, a subset of SCI patients and animals do not display neuropathic pain, suggesting the involvement of epigenetic changes. This study investigates the hypotheses that (1) GABAergic neurons undergo mitochondrial dysfunction upon glutamate stimulation and (2) there are differences in the epigenetic profiles between SCI rats with different sensitivity. Neural progenitor cells of E14 Sprague-Dawley rat embryos and human induced pluripotent stem cells were processed towards GABAergic phenotype. Both cell lines were exposed to different glutamate concentrations, followed by analyses of mitochondrial viability, ATP levels, and GABA production. Spinal cord tissues from SCI rats with different pain threshold were immunostained with H3 methylation antibodies. Glutamate stimulation led to a dose-dependent reduction in mitochondrial viability in both cell lines, along with decreased production of ATP and GABA in cell lysate. H3K27 trimethylation markers were upregulated in more sensitive SCI animals compared to less sensitive groups. The preliminary results indicate that mitochondrial dysfunction due to glutamate stimulation might contribute to GABAergic disinhibition and suggest the role of H3K27 methylation in chronic pain maintenance. Future research will focus on developing targeted interventions to inhibit mitochondrial damage and reverse epigenetic changes post-SCI to prevent or alleviate chronic pain development.
