16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice
Abstract
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 16p11.2 df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2 df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2 df/+ 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 16p11.2 df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2 df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2 df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses.
Related
- Mitochondrial PEX14 supports peroxisome biogenesis
- Ginsenoside Rg1 reduces endothelial cell injury in transplant-associated thromboticmicroangiopathy by regulating the expression of HIF-1α
- Integrative bulk and single-cell transcriptomics links amino acid metabolism-related biomarkers to endothelial immune remodeling in periodontitis
- Cellular and mitochondrial correlates of regional glucose metabolism in the human cortex
- AMPK reinforces mitochondrial metabolism and suppresses pathological remodeling in Complex V-deficient cardiomyocytes
BibTeX
@article{belandmillar202616p112,
title = {{16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice}},
author = {Alexandria Béland-Millar and Alexia Kirby and Yen Truong and Julie Ouellette and Sozerko Yandiev and Khalil Bouyakdan and Chantal Pileggi and Shama Naz and Melissa Yin and Micaël Carrier and Pavel Kotchetkov and Marie-Kim St-Pierre and Marie-Ève Tremblay and Julien Courchet and Mary-Ellen Harper and Thierry Alquier and Claude Messier and Adam Shuhendler and Baptiste Lacoste},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2023.112485},
url = {https://hal.science/hal-05791053v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 16p11.2 haploinsufficiency reduces mitochondrial biogenesis in brain endothelial cells and alters brain metabolism in adult mice
AU - Alexandria Béland-Millar
AU - Alexia Kirby
AU - Yen Truong
AU - Julie Ouellette
AU - Sozerko Yandiev
AU - Khalil Bouyakdan
AU - Chantal Pileggi
AU - Shama Naz
AU - Melissa Yin
AU - Micaël Carrier
AU - Pavel Kotchetkov
AU - Marie-Kim St-Pierre
AU - Marie-Ève Tremblay
AU - Julien Courchet
AU - Mary-Ellen Harper
AU - Thierry Alquier
AU - Claude Messier
AU - Adam Shuhendler
AU - Baptiste Lacoste
PY - 2026
DA - 2026/10/10
JO - Cell Reports
DO - 10.1016/j.celrep.2023.112485
UR - https://hal.science/hal-05791053v1
AB - 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 16p11.2 df/+ mice affect brain metabolism is unknown. Here, we report that anesthetized 16p11.2 df/+ mice display elevated brain glucose uptake, a phenomenon recapitulated in mice with endothelial-specific 16p11.2 haplodeficiency. Awake 16p11.2 df/+ 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 16p11.2 df/+ mice that also display reduced mitochondria number in brain endothelial cells. This is not associated with changes in mitochondria fusion or fission proteins, but 16p11.2 df/+ brain endothelial cells lack the splice variant NT-PGC-1α, suggesting defective mitochondrial biogenesis. We propose that altered brain metabolism in 16p11.2 df/+ mice is compensatory to endothelial dysfunction, shedding light on previously unknown adaptative responses.
SN - 2211-1247
SN - 2211-1247
ER -