2026-03-14T20:06:06Z https://hirosaki.repo.nii.ac.jp/oai

oai:hirosaki.repo.nii.ac.jp:02000354 2025-10-20T04:29:59Z 557:1754615242943:561:1713851803406

Benzodiazepine-induced cell growth inhibition via GABAA receptor- and TSPO-independent pathways Shimoyama, Shuji Furukawa, Tomonori Ueno, Shinya open access GABAA receptor TSPO benzodiazepine cell cycle Our previous study showed that chronic administration of diazepam （DZP） induces changes in gene expression in the hippocampus, cortex, and amygdala. Pathway analysis indicated that cell cycle was altered by chronic DZP treatment. These results raise the concern that chronic DZP administration provokes alterations in cell proliferation. The aim of this study is to elucidate the mechanism by which benzodiazepines（ BZDs） regulate cell cycle. Cell growth curve analysis and MTT assays revealed that DZP treatment significantly reduced cell growth in the microglial cell line. Interestingly, cell growth was not affected by antagonizing the DZP target molecules, gammaaminobutyric acid （GABA） Type A receptor （GABAA-R）, and 18 kDa translocator protein （TSPO）. Similar to the results of DZP, other BZDs such as lorazepam （LZP） and midazolam （MDZ） showed a significant decrease in cell growth. In addition to the mouse microglial cell line results, mouse neuroblastoma cell line also showed an inhibition of cell growth. In contrast, only MDZ inhibited cell growth in human astrocytoma cell line, U373 cells. However, it is not clear whether these differences depend on species or cell types. Consequently, BZDs inhibit cell growth via GABAA-R- and TSPO-independent pathways. 弘前大学大学院医学研究科 2024-03-28 eng journal article VoR http://hdl.handle.net/10129/0002000354 https://hirosaki.repo.nii.ac.jp/records/2000354 AN00211444 2434-4656 弘前医学 Hirosaki Medical Journal 74 1-4 52 60 https://hirosaki.repo.nii.ac.jp/record/2000354/files/Hirosaki Med J 74-1-4_52.pdf application/pdf 594 KB 2024-04-29