The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment.
J Proteome Res
; 22(9): 2936-2949, 2023 09 01.
Article
em En
| MEDLINE
| ID: mdl-37611228
ABSTRACT
Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Disfunção Cognitiva
/
Distúrbios do Início e da Manutenção do Sono
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article