Date of Award
2025
Degree Type
Thesis
Degree Name
Master of Science in Interdisciplinary Neurosciences
Department
Biological Sciences
First Advisor
Katharina Quilan
Abstract
Cerebral palsy often results from perinatal hypoxia-ischemia and is characterized by motor and sensory dysfunction associated with altered serotonergic signaling in the spinal cord. The 5-HT₇ receptor, a G-protein-coupled receptor implicated in both motor control and nociceptive modulation, may thus play a critical role in these post-injury changes. However, the regional and developmental patterns of expression of 5-HT7 following HI injury are not well understood.
In this study, we investigated the expression of spinal 5-HTR7 in a neonatal rabbit model of HI injury at P1, P5, and P8 using Western blot analyses normalized to total protein. Tissue was isolated from the dorsal and ventral horns of both cervical and lumbar spinal cord segments. Spinal roots and dorsal root ganglia were removed before homogenization to ensure central specificity. Immunohistochemical labeling with DAPI confirmed accurate dorsal-ventral separation and regional integrity.
Interestingly, across developmental stages, 5-HTR7 showed a pattern of dorsal upregulation and ventral downregulation following HI injury compared to sham controls. Whereas many comparisons did not reach statistical significance, at P8 there was a significant reduction (p < 0.05) in the lumbar ventral horn of 5-HTR7 expression. Effect size and post-hoc power analyses revealed moderate-to-large magnitudes for the most salient effects (Hedges' g ³ 0.5), while achieved power was fairly low in most analyses. However, these trends may be biologically meaningful despite sample size limitations.
These findings suggest that hypoxia-ischemia results in region-specific and developmentally dynamic changes in the expression of spinal 5-HTR7, with reduced receptor levels in motor-associated regions and increased expression in sensory domains. Such divergent modulation may point to neuronal losses, inflammatory signaling, or compensatory serotonergic sprouting within the spinal cord. These studies collectively support a model wherein dysregulation of 5-HTR7 contributes to a disruption in motor and sensory integration after perinatal HI injury and support the potential therapeutic relevance of targeting the serotonergic system in CP.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Santos, Tracy, "ALTERATIONS OF SEROTONIN RECEPTOR 7 EXPRESSION IN THE SPINAL CORD IN A MODEL OF CEREBRAL PALSY" (2025). Open Access Master's Theses. Paper 2686.
https://digitalcommons.uri.edu/theses/2686