دورية أكاديمية
16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice
| العنوان: | 16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice |
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| المؤلفون: | Béland-Millar, Alexandria, Kirby, Alexia, Truong, Yen, Ouellette, Julie, Yandiev, Sozerko, Bouyakdan, Khalil, Pileggi, Chantal, Naz, Shama, Yin, Melissa, Carrier, Micaël, Kotchetkov, Pavel, St-Pierre, Marie-Kim, Tremblay, Marie-Ève, Courchet, Julien, Harper, Mary-Ellen, Alquier, Thierry, Messier, Claude, Shuhendler, Adam J., Lacoste, Baptiste |
| بيانات النشر: | Cell Reports |
| سنة النشر: | 2023 |
| المجموعة: | University of Victoria (Canada): UVicDSpace |
| مصطلحات موضوعية: | autism, endothelium, 16p11.2 deletion, metabolism, brain, glucose, lactate, mouse, mitochondrion |
| الوصف: | We thank Carlie Boisvert (Lacoste lab) for technical assistance and Andrew Heinmiller (Fujifilm VisualSonics) for guidance on photoacoustic imaging. We thank the CRCHUM rodent metabolic phenotyping core facility for their help with tolerance tests. ; Summary Neurovascular abnormalities in mouse models of 16p11.2 deletion autism syndrome are reminiscent of alterations reported in murine models of glucose transporter deficiency, including reduced brain angiogenesis and behavioral alterations. Yet, whether cerebrovascular alterations in 16p11.2df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2df/+ mice display attenuated relative fluctuations of extracellular brain glucose following systemic glucose administration. Targeted metabolomics on cerebral cortex extracts reveals enhanced metabolic responses to systemic glucose in 16p11.2df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses. ; Metabolites were analyzed at the University of Ottawa Metabolomics Core Facility; this facility is supported by the Terry Fox Foundation and Ottawa University. B.L. was supported by start-up funds from the Ottawa Hospital Research Institute, a Canadian Institutes of Health Research (grant #388805), an award from The Scottish Rite Charitable Foundation of Canada (grant #17112), and a J.P. Bickell Foundation medical research grant. Part of this work is also funded by an Autism Research Program Idea Development Award from the US Department of Defense office of the ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Béland-Millar, A., Kirby, A., Truong, Y., Ouellette, J., Yandiev, S., Bouyakdan, K., . Lacoste, B. (2023). 16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice. Cell Reports, 42(5), 112485. https://doi.org/10.1016/j.celrep.2023.112485Test; https://doi.org/10.1016/j.celrep.2023.112485Test; http://hdl.handle.net/1828/15598Test |
| DOI: | 10.1016/j.celrep.2023.112485 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2023.112485Test http://hdl.handle.net/1828/15598Test |
| رقم الانضمام: | edsbas.48BAB4AA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2023.112485 |
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