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Peer-reviewedCC BY 4.0Science Advances

Common transcriptional changes in the brain during hibernation and Alzheimer’s disease

  • Pablo Largo-Barrientos1,2
  • Roman Praschberger1,2,3
  • Gonzalo León-Espinosa4
  • Pieter-Jan Bultynck1,2
  • Anastasia Mallopoulou1,2
  • João F. Machado1,2
  • Suresh Poovathingal1,2
  • Kristofer Davie1,2
  • Patrik Verstreken1,2
4 affiliations
  1. 1VIB-KU Leuven Center for Neuroscience; Leuven, Belgium.
  2. 2KU Leuven, Department of Neurosciences, Leuven Brain Institute, Mission Lucidity; Leuven, Belgium.
  3. 3Medical University of Innsbruck, Institute of Human Genetics; Innsbruck, Austria.
  4. 4Universidad San Pablo-Centro de Estudios Universitarios, Facultad de Farmacia, Departamento de Química y Bioquímica; Madrid, Spain.
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Abstract

Hibernation demands rapid brain adaptations, involving cycles of reduced metabolic rate during torpor, followed by brief periods of arousal. Previous studies show hibernation induces a drastic increase in Tau hyperphosphorylation, but a mechanistic connection to disease remains unclear. Using single-nucleus RNA sequencing on hippocampi of golden hamsters, we unveil large transcriptional shifts across the hibernation cycle in all cell types, especially glia. Common transcriptional changes in mitochondrial and ribosomal genes are observed in all different cell types. In addition, hibernation triggers an inflammatory-like response in microglia that in part resembles cell states observed in Alzheimer’s disease, but here in the absence of Aβ-accumulation and neurodegeneration. These findings reveal brain transformations that might help preserve vital functions under extreme conditions and they suggest that early cellular changes in AD may be a natural adaptive process.

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Cite

BibTeXRIS
BibTeX
@article{largobarrientos2026common,
  title = {{Common transcriptional changes in the brain during hibernation and Alzheimer’s disease}},
  author = {Pablo Largo-Barrientos and Roman Praschberger and Gonzalo León-Espinosa and Pieter-Jan Bultynck and Anastasia Mallopoulou and João F. Machado and Suresh Poovathingal and Kristofer Davie and Patrik Verstreken},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aeg3486},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aeg3486},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Common transcriptional changes in the brain during hibernation and Alzheimer’s disease
AU  - Pablo Largo-Barrientos
AU  - Roman Praschberger
AU  - Gonzalo León-Espinosa
AU  - Pieter-Jan Bultynck
AU  - Anastasia Mallopoulou
AU  - João F. Machado
AU  - Suresh Poovathingal
AU  - Kristofer Davie
AU  - Patrik Verstreken
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aeg3486
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aeg3486
AB  - Hibernation demands rapid brain adaptations, involving cycles of reduced metabolic rate during torpor, followed by brief periods of arousal. Previous studies show hibernation induces a drastic increase in Tau hyperphosphorylation, but a mechanistic connection to disease remains unclear. Using single-nucleus RNA sequencing on hippocampi of golden hamsters, we unveil large transcriptional shifts across the hibernation cycle in all cell types, especially glia. Common transcriptional changes in mitochondrial and ribosomal genes are observed in all different cell types. In addition, hibernation triggers an inflammatory-like response in microglia that in part resembles cell states observed in Alzheimer’s disease, but here in the absence of Aβ-accumulation and neurodegeneration. These findings reveal brain transformations that might help preserve vital functions under extreme conditions and they suggest that early cellular changes in AD may be a natural adaptive process.
SN  - 2375-2548
ER  -