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.

• Keywords
• amyloid precursor protein, behavior, brain morphology, brain repair, gene expression, transcription, translation, traumatic brain injury,
• MeSH
• Amyloid beta-Protein Precursor * genetics   MeSH
• Disease Models, Animal MeSH
• Brain * metabolism   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Brain Injuries * metabolism   genetics   pathology   MeSH
• Proteome * metabolism   MeSH
• Proteomics MeSH
• Transcriptome * MeSH
• Brain Injuries, Traumatic * metabolism   genetics   pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amyloid beta-Protein Precursor * MeSH
• Proteome * MeSH