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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F25%3A73631681" target="_blank" >RIV/61989592:15110/25:73631681 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/25:00144422 RIV/00159816:_____/25:00082308

Výsledek na webu

<a href="https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70093" target="_blank" >https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70093</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/alz.70093" target="_blank" >10.1002/alz.70093</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.METHODSWe 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.RESULTSAfter 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.DISCUSSIONThe 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.METHODSWe 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.RESULTSAfter 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.DISCUSSIONThe 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Alzheimers &amp; Dementia

ISSN

1552-5260

e-ISSN

1552-5279

Svazek periodika

21

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

"e70093"

Kód UT WoS článku

001484191800017

EID výsledku v databázi Scopus

2-s2.0-105003800260