Zebrafish brain RNA sequencing reveals that cell adhesion molecules are critical in brain aging

Abstract

Brain aging is a complex process, which involves multiple pathways including various components from cellular to molecular. This study aimed to investigate the gene expression changes in zebrafish brains through young-adult to adult, and adult to old age. RNA sequencing was performed on isolated neuronal cells from zebrafish brains. The cells were enriched in progenitor cell markers, which are known to diminish throughout the aging process. We found 176 statistically significant, differentially expressed genes among the groups, and identified a group of genes based on gene ontology descriptions, which were classified as cell adhesion molecules. The relevance of these genes was further tested in another set of zebrafish brains, human healthy, and Alzheimer's disease brain samples, as well as in Allen Brain Atlas data. We observed that the expression change of 2 genes, GJC2 and ALCAM, during the aging process was consistent in all experimental sets. Our findings provide a new set of markers for healthy brain aging and suggest new targets for therapeutic approaches to neurodegenerative diseases.

High-fat diet feeding triggers a regenerative response in the adult zebrafish brain

“…Interestingly, there was a decrease in the oligodendrocyte marker oligodendrocyte transcription factor ( olig2 ) and the neuronal markers neuronal differentiation 1 ( neuroD1 ), ELAV-like neuron-specific RNA binding protein 4 ( HuD ), and Rbfox3a ( neun ) in response to short-term HFD and a remarkable recovery after long-term HFD, proposing that the dying oligodendrocytes and neurons were replaced with the newborn ones (Figure 3E). Since these genes are expressed in mature neurons in the adult zebrafish brain (Kroehne et al, 2011; Dohaku et al, 2019; Erbaba et al, 2020; Shimizu et al, 2021), our data suggest that HFD results in neuronal cell death, glial cell activation and induction of a regenerative response in the brain. Together, these data indicate that HFD triggers inflammation, apoptosis, and proliferation not only in the liver but also in the brain and reactive neurogenesis in the brain.…”

Effects of caloric restriction on the antagonistic and integrative hallmarks of aging

“…Neurogenesis continues in a limited fashion into adult life with a decreased rate as compared to earlier developmental periods and being restricted to some discrete areas of the mammalian brain, i.e., subventricular zone (SVZ) of the lateral ventricle, the dentate gyrus of the hippocampus and rostral migratory stream of the olfactory bulb (Eriksson et al, 1998;Apple et al, 2017;Ming and Song, 2011;Taupin, 2006). We also recently showed via RNA sequencing and qPCR validations that stem cell markers were significantly decreasing in the brains of zebrafish with advancing age (Erbaba et al, 2020). Therefore an inverse relationship between aging and stem cell functioning appears to exist.…”