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

Varování

Publikace nespadá pod Ústav výpočetní techniky, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	LACOVICH STRAŠIL Valentina CARNA Maria NOVOTNY Sebastian J. WANG Shanshan TEXLOVA Katerina KOVACOVICOVA Kristina Locker DRAGISIC Neda HAVAS Daniel HEAD Brian P. GEDA Yonas E. LIMBACK-STOKIN Clara STOKIN Gorazd Bernard
Rok publikování	2025
Druh	Článek v odborném periodiku
Časopis / Zdroj	ALZHEIMERS & DEMENTIA
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70093
Doi	https://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.
Související projekty:	ADAR RNA editing, how immune systems and brains breach The Central Dogma