Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury
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Rok publikování | 2025 |
Druh | Článek v odborném periodiku |
Časopis / Zdroj | ALZHEIMERS & DEMENTIA |
Fakulta / Pracoviště MU | |
Citace | |
www | https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70093 |
Doi | http://dx.doi.org/10.1002/alz.70093 |
Klíčová slova | amyloid precursor protein; behavior; brain morphology; brain repair; gene expression; transcription; translation; traumatic brain injury |
Popis | 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 or 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. |
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