Hippocampal neurons respond to brain activity with functional hypoxia

2021-02-09 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Hippocampal neurons respond to brain activity with functional hypoxia​
Butt, U. J.; Steixner-Kumar, A. A.; Depp, C.; Sun, T.; Hassouna, I.; Wüstefeld, L. & Arinrad, S. et al.​ (2021) 
Molecular Psychiatry26(6) pp. 1790​-1807​.​ DOI: https://doi.org/10.1038/s41380-020-00988-w 

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Butt, Umer Javed; Steixner-Kumar, Agnes A.; Depp, Constanze; Sun, Ting; Hassouna, Imam; Wüstefeld, Liane; Arinrad, Sahab; Zillmann, Matthias R.; Schopf, Nadine; Fernandez Garcia-Agudo, Laura; Mohrmann, Leonie; Bode, Ulli; Ronnenberg, Anja; Hindermann, Martin; Goebbels, Sandra; Bonn, Stefan; Katschinski, Dörthe M.; Miskowiak, Kamilla W.; Nave, Klaus-Armin; Ehrenreich, Hannelore
Physical activity and cognitive challenge are established non-invasive methods to induce comprehensive brain activation and thereby improve global brain function including mood and emotional well-being in healthy subjects and in patients. However, the mechanisms underlying this experimental and clinical observation and broadly exploited therapeutic tool are still widely obscure. Here we show in the behaving brain that physiological (endogenous) hypoxia is likely a respective lead mechanism, regulating hippocampal plasticity via adaptive gene expression. A refined transgenic approach in mice, utilizing the oxygen-dependent degradation (ODD) domain of HIF-1α fused to CreERT2 recombinase, allows us to demonstrate hypoxic cells in the performing brain under normoxia and motor-cognitive challenge, and spatially map them by light-sheet microscopy, all in comparison to inspiratory hypoxia as strong positive control. We report that a complex motor-cognitive challenge causes hypoxia across essentially all brain areas, with hypoxic neurons particularly abundant in the hippocampus. These data suggest an intriguing model of neuroplasticity, in which a specific task-associated neuronal activity triggers mild hypoxia as a local neuron-specific as well as a brain-wide response, comprising indirectly activated neurons and non-neuronal cells.
Issue Date
Molecular Psychiatry 
TRR 274: Checkpoints of Central Nervous System Recovery 
TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease 
SFB 1286: Quantitative Synaptologie 
SFB 1286 | Z02: Integrative Datenanalyse und -interpretation. Generierung einer synaptisch-integrativen Datenstrategie (SynIDs) 
Working Group
RG Ehrenreich (Clinical Neuroscience) 
RG Nave (Neurogenetics) 
RG Bonn 
External URL
Max-Planck-Gesellschaft (Max Planck Society) https://doi.org/10.13039/501100004189
National University of Sciences and Technology (NUST) https://doi.org/10.13039/501100007278
Boehringer Ingelheim Stiftung (Boehringer Ingelheim Foundation) https://doi.org/10.13039/501100008454
SFB 1286 Project Z2
Lundbeckfonden (Lundbeck Foundation) https://doi.org/10.13039/501100003554
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Dr. Miriam & Sheldon G. Adelson Medical Research Foundation) https://doi.org/10.13039/100005984



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