Brainstem cytokine changes in healthy ageing and Motor Neurone Disease

Tennakoon, Anuradha; Katharesan, Viythia; Johnson, Ian

doi:10.1016/j.jns.2017.08.013

Cited by 2 publications

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to Itgax, Cxcl10, a chemokine superfamily coding protein, is expressed in astrocytes, glial cells, dendritic cells, and neutrophils, and is closely related to neuroinflammation ( Fazia et al, 2020 ). Cxcl10 is upregulated in aged brains ( Hasegawa-Ishii et al, 2016 ; Palomera-Ávalos et al, 2017 ; Tennakoon et al, 2017 ; Hu et al, 2019 ). Expression of Cxcl10 can induce the release of the senescence-associated secretory phenotype, which consists of multiple inflammatory factors and promotes brain aging ( Cardoso et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring molecular signatures related to the mechanism of aging in different brain regions by integrated bioinformatics

Xie²,

Li³

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The mechanism of brain aging is not fully understood. Few studies have attempted to identify molecular changes using bioinformatics at the subregional level in the aging brain. This study aimed to identify the molecular signatures and key genes involved in aging, depending on the brain region. Differentially expressed genes (DEGs) associated with aging of the cerebral cortex (CX), hippocampus (HC), and cerebellum (CB) were identified based on five datasets from the Gene Expression Omnibus (GEO). The molecular signatures of aging were explored using functional and pathway analyses. Hub genes of each brain region were determined by protein–protein interaction network analysis, and commonly expressed DEGs (co-DEGs) were also found. Gene–microRNAs (miRNAs) and gene–disease interactions were constructed using online databases. The expression levels and regional specificity of the hub genes and co-DEGs were validated using animal experiments. In total, 32, 293, and 141 DEGs were identified in aging CX, HC, and CB, respectively. Enrichment analysis indicated molecular changes related to leukocyte invasion, abnormal neurotransmission, and impaired neurogenesis due to inflammation as the major signatures of the CX, HC, and CB. Itgax is a hub gene of cortical aging. Zfp51 and Zfp62 were identified as hub genes involved in hippocampal aging. Itgax and Cxcl10 were identified as hub genes involved in cerebellar aging. S100a8 was the only co-DEG in all three regions. In addition, a series of molecular changes associated with inflammation was observed in all three brain regions. Several miRNAs interact with hub genes and S100a8. The change in gene levels was further validated in an animal experiment. Only the upregulation of Zfp51 and Zfp62 was restricted to the HC. The molecular signatures of aging exhibit regional differences in the brain and seem to be closely related to neuroinflammation. Itgax, Zfp51, Zfp62, Cxcl10, and S100a8 may be key genes and potential targets for the prevention of brain aging.

show abstract