Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice

P. Bielefeld, A. Martirosyan, S. Martín-Suárez, A. Apresyan, G. F. Meerhoff, F. Pestana, S. Poovathingal, N. Reijner, W. Koning, R. A. Clement, I. Veen, E. M. Toledo, O. Polzer, I. Durá, S. Hovhannisyan, B. S. Nilges, A. Bogdoll, N. D. Kashikar, P. J. Lucassen, T. G. Belgard, J. M. Encinas, M. G. Holt () and C. P. Fitzsimons ()
Additional contact information
P. Bielefeld: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
A. Martirosyan: VIB Center for Brain and Disease Research
S. Martín-Suárez: Barrio Sarriena S/N
A. Apresyan: Armenian Bioinformatics Institute
G. F. Meerhoff: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
F. Pestana: VIB Center for Brain and Disease Research
S. Poovathingal: VIB Center for Brain and Disease Research
N. Reijner: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
W. Koning: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
R. A. Clement: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
I. Veen: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
E. M. Toledo: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
O. Polzer: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
I. Durá: Barrio Sarriena S/N
S. Hovhannisyan: Yerevan State University
B. S. Nilges: Resolve Biosciences GmbH
A. Bogdoll: Resolve Biosciences GmbH
N. D. Kashikar: Resolve Biosciences GmbH
P. J. Lucassen: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam
T. G. Belgard: The Bioinformatics CRO
J. M. Encinas: Barrio Sarriena S/N
M. G. Holt: VIB Center for Brain and Disease Research
C. P. Fitzsimons: Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits. The adult hippocampus harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, it is not known how TBI may affect hippocampal astrogliogenesis. Using a controlled cortical impact model of TBI in male mice, single cell RNA sequencing and spatial transcriptomics, we assessed how TBI affected hippocampal NSCs and the neuronal and astroglial lineages derived from them. We observe an increase in NSC-derived neuronal cells and a concomitant decrease in NSC-derived astrocytic cells, together with changes in gene expression and cell dysplasia within the dentate gyrus. Here, we show that TBI modifies NSC fate to promote neurogenesis at the cost of astrogliogenesis and identify specific cell populations as possible targets to counteract TBI-induced cellular changes in the adult hippocampus.

Date: 2024
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DOI: 10.1038/s41467-024-49299-6

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