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Grade, S. ; Thomas, J. ; Zarb, Y. ; Thorwirth, M. ; Conzelmann, K.K.* ; Hauck, S.M. ; Götz, M.

Brain injury environment critically influences the connectivity of transplanted neurons.

Sci. Adv. 8:eabg9445 (2022)
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Open Access Gold
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Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration, and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative monosynaptic rabies virus (RABV) tracing unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain versus exuberant after TBI. In the latter, the initial overshoot is followed by pruning, with only a few input neurons persisting at 3 months. Proteomic profiling identifies candidate molecules for regulation of the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Quellenangaben Volume: 8, Issue: 23, Pages: , Article Number: eabg9445 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed