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Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury

V. Lacovich, M. Čarna, SJ. Novotný, S. Wang, K. Texlová, KL. Kovačovicova, N. Dragišić, D. Havas, BP. Head, YE. Geda, C. Limbäck-Stokin, GB. Stokin

. 2025 ; 21 (4) : e70093. [pub] -

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25016204

Grantová podpora
CZ.02.1.01/0.0/0.0/16_019/0000868 European Regional Development Funds
CZ.02.1.01/0.0/0.0/17_043/0009632 European Union's Horizon 2020
CZ.02.1.01/0.0/0.0/15_003/0000492 CETOCOEN EXCELLENCE
5I01BX003671 VA Merit
1IK6BX006318 VA Research Career Scientist Award
21-27329X Czech Science Foundation (GAČR)
LX22NPO5107 (MEYS) European Union: Next Generation EU - Project National Institute for Neurological Research

INTRODUCTION: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. METHODS: We assessed brain morphology (n = 4-9 mice/group), transcriptome (n = 3 mice/group), proteome (n = 3 mice/group), and behavior (n = 17-27 mice/group) of wild-type (WT) and APP knock-out (KO) mice either untreated or 10-weeks following TBI. RESULTS: After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI. DISCUSSION: The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury. HIGHLIGHTS: 10-weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair. Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair. APP responds to TBI by changes in gene expression at a transcriptional and translational level. APP deficiency precludes molecular brain changes in response to TBI.

Citace poskytuje Crossref.org

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