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Wang XL, Kooijman S, Gao Y, et al. Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity. Mol Psychiatry. 2021;26(11):6336-6349doi: 10.1038/s41380-021-01169-z.
Wang, X. L., Kooijman, S., Gao, Y., Tzeplaeff, L., Cosquer, B., Milanova, I., Wolff, S. E. C., Korpel, N., Champy, M. F., Petit-Demoulière, B., Goncalves Da Cruz, I., Sorg-Guss, T., Rensen, P. C. N., Cassel, J. C., Kalsbeek, A., Boutillier, A. L., & Yi, C. X. (2021). Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity. Molecular psychiatry, 26(11), 6336-6349. https://doi.org/10.1038/s41380-021-01169-z
Wang, Xiao-Lan, et al. "Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity." Molecular psychiatry vol. 26,11 (2021): 6336-6349. doi: https://doi.org/10.1038/s41380-021-01169-z
Wang XL, Kooijman S, Gao Y, Tzeplaeff L, Cosquer B, Milanova I, Wolff SEC, Korpel N, Champy MF, Petit-Demoulière B, Goncalves Da Cruz I, Sorg-Guss T, Rensen PCN, Cassel JC, Kalsbeek A, Boutillier AL, Yi CX. Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity. Mol Psychiatry. 2021 Nov;26(11):6336-6349. doi: 10.1038/s41380-021-01169-z. Epub 2021 May 28. PMID: 34050326.
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Mol Psychiatry. 2021 Nov;26(11):6336-6349. doi: 10.1038/s41380-021-01169-z. Epub 2021 May 28.

Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity.

Molecular psychiatry

Xiao-Lan Wang, Sander Kooijman, Yuanqing Gao, Laura Tzeplaeff, Brigitte Cosquer, Irina Milanova, Samantha E C Wolff, Nikita Korpel, Marie-France Champy, Benoit Petit-Demoulière, Isabelle Goncalves Da Cruz, Tania Sorg-Guss, Patrick C N Rensen, Jean-Christophe Cassel, Andries Kalsbeek, Anne-Laurence Boutillier, Chun-Xia Yi

Affiliations

  1. Université de Strasbourg, Laboratoire de Neuroscience Cognitives et Adaptatives (LNCA), Strasbourg, France.
  2. Department of Endocrinology and Metabolism, Amsterdam University Medical Centres (UMC), University of Amsterdam, Amsterdam, The Netherlands.
  3. Laboratory of Endocrinology, Amsterdam University Medical Centres (UMC), University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands.
  4. Department of Medicine, Divison of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
  5. CNRS UMR 7364, LNCA, Strasbourg, France.
  6. Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
  7. PHENOMIN-ICS, Institut Clinique de la souris, CNRS, UMR7104, Illkirch, France.
  8. INSERM, U964, Illkirch, France.
  9. Université de Strasbourg, Strasbourg, France.
  10. Université de Strasbourg, Laboratoire de Neuroscience Cognitives et Adaptatives (LNCA), Strasbourg, France. [email protected].
  11. CNRS UMR 7364, LNCA, Strasbourg, France. [email protected].
  12. Department of Endocrinology and Metabolism, Amsterdam University Medical Centres (UMC), University of Amsterdam, Amsterdam, The Netherlands. [email protected].
  13. Laboratory of Endocrinology, Amsterdam University Medical Centres (UMC), University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands. [email protected].
  14. Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. [email protected].

PMID: 34050326 DOI: 10.1038/s41380-021-01169-z

Abstract

Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-down of the core clock gene, Bmal1, resulted in increased microglial phagocytosis in mice subjected to high-fat diet (HFD)-induced metabolic stress and likewise among mice engaged in critical cognitive processes. Enhanced microglial phagocytosis was associated with significant retention of pro-opiomelanocortin (POMC)-immunoreactivity in the mediobasal hypothalamus in mice on a HFD as well as the formation of mature spines in the hippocampus during the learning process. This response ultimately protected mice from HFD-induced obesity and resulted in improved performance on memory tests. We conclude that loss of the rigorous control implemented by the intrinsic clock machinery increases the extent to which microglial phagocytosis can be triggered by neighboring neurons under metabolic stress or during memory formation. Taken together, microglial responses associated with loss of Bmal1 serve to ensure a healthier microenvironment for neighboring neurons in the setting of an adaptive response. Thus, microglial Bmal1 may be an important therapeutic target for metabolic and cognitive disorders with relevance to psychiatric disease.

© 2021. The Author(s).

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