▲Professor Gyeong-ok Cho, Department of Pharmacology, Catholic University of Korea.
[메디칼업저버 박선혜 기자] A national research team has discovered, for the first time in the country, target cells that specialize in the cognitive dysfunction that accompanies epilepsy.
The research team led by Professor Cho Kyung-ok (corresponding author, Catholic Brain and Neuroscience Research Institute) and Dr. Inyoung Choi (first author) from the Department of Pharmacology of the Catholic University of Korea succeeded in discovering new effective target cells in treatment of cognitive dysfunction that accompanies epilepsy.
This target cell is LIN28A, a protein that increases in the hippocampus after a seizure. The research team focused on LIN28A, a protein activated in the hippocampus after an epileptic seizure. The hippocampus is a part of the brain that plays an important role in memory and learning, and it has been determined that when LIN28A increases after a seizure, abnormal neurons are produced and cognitive impairment occurs.
In a previous study, the research team confirmed that suppressing the production of abnormal neurons can improve the cognitive dysfunction that accompanies epilepsy, and through this follow-up study, they discovered a treatment target cell called LIN28A.
As a result of deletion of the LIN28A protein using transgenic mice, it was confirmed that cognitive impairment after seizures was improved. Furthermore, when only LIN28A expression was blocked without inducing seizures, no difference in cognitive impairment was found, revealing that LIN28A is a specialized molecular target for the cognitive impairment that accompanies epilepsy.
In this study, an immunostaining method used to detect specific proteins using antigen-antibody reactions against proteins targeting the dentate gyrus (hilum) tissue of the hippocampus was used to detect granule cells produced in a manner abnormal after seizures, which are significant when blocking the expression of LIN28A. which has decreased significantly.
Furthermore, as a result of examining transcriptome analysis and RNA/protein expression to discover downstream molecular biological target cells modified by LIN28A, mice with LIN28A-deficient epilepsy showed changes in the expression of serotonin receptors such as HTR4, HTR2C and HTR1B compared to control mice with epilepsy was clearly observed. Notably, HTR4 was expressed in LIN28A-expressing cells in the area where neural stem cells are primarily located.
▲Pattern of increased LIN28A expression after epileptic seizure, relief of cognitive function accompanying epilepsy due to LIN28A deletion, and neurobiological mechanism.
Professor Gyeong-ok Cho said: “Among the various comorbid conditions associated with epilepsy, patients with temporal lobe epilepsy suffering from cognitive dysfunction are the most common,” adding: “The LIN28A discovered through this study will throw the basis for the development of a treatment for the cognitive dysfunction that accompanies epilepsy, which is an intractable disease in the future.” “We will be able to provide it,” he said.
Meanwhile, this research was conducted with the support of the Korean National Research Foundation’s Mid-Career Researchers Support Project, Basic Laboratory Project, Creative Challenges Research-based Support Project, and Technology Development Project of the Korea Health Industry Development Institute to solve problems in the clinical setting. fields of brain and nervous system diseases of the Korea Health Industry Development Institute. The research findings were published in the latest issue of JCI insight, an international journal in the field of translational research and sister journal to the Journal of Clinical Investigation.
2024-01-22 00:52:51
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