Author:
Komiyama Kazuki,Iijima Keiya,Kawabata-Iwakawa Reika,Fujihara Kazuyuki,Kakizaki Toshikazu,Yanagawa Yuchio,Yoshimoto Yuhei,Miyata Shigeo
Abstract
AbstractPatients with glioma often demonstrate epilepsy. We previously found burst discharges in the peritumoral area in patients with malignant brain tumors during biopsy. Therefore, we hypothesized that the peritumoral area may possess an epileptic focus and that biological alterations in the peritumoral area may cause epileptic symptoms in patients with glioma. To test our hypothesis, we developed a rat model of glioma and characterized it at the cellular and molecular levels. We first labeled rat C6 glioma cells with tdTomato, a red fluorescent protein (C6-tdTomato), and implanted them into the somatosensory cortex of VGAT-Venus rats, which specifically expressed Venus, a yellow fluorescent protein in GABAergic neurons. We observed that the density of GABAergic neurons was significantly decreased in the peritumoral area of rats with glioma compared with the contralateral healthy side. By using a combination technique of laser capture microdissection and RNA sequencing (LCM-seq) of paraformaldehyde-fixed brain sections, we demonstrated that 19 genes were differentially expressed in the peritumoral area and that five of them were associated with epilepsy and neurodevelopmental disorders. In addition, the canonical pathways actively altered in the peritumoral area were predicted to cause a reduction in GABAergic neurons. These results suggest that biological alterations in the peritumoral area may be a cause of glioma-related epilepsy.
Funder
Japan Society for the Promotion of Science
the Fostering Health Professionals for Changing Needs of Cancer by MEXT of Japan and Gunma University Initiative for Advanced Research
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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