Dataset Information

Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain.

ABSTRACT: Transfer RNA-derived fragments (tRFs) are known to contribute to multiple illnesses, including cancers, viral infections, and age-related neurodegeneration. In this study, we used senescence-accelerated mouse prone 8 (SAMP8) as a model of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, and a control, the senescence-accelerated mouse resistant 1 (SAMR1) model, to comprehensively explore differences in tRF expression between them. We discovered 570 tRF transcripts among which eight were differentially expressed. We then obtained 110 potential target genes in a miRNA-like pattern. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation suggest that these target genes participate in a variety of brain functions; e.g., synapse formation (GO: 0045202) and the synaptic vesicle cycle pathway. We further assessed in detail those tRFs whose miRNA-like pattern was most likely to promote the progression of either Alzheimer's or Parkinson's disease, such as AS-tDR-011775 acting on Mobp and Park2. Our findings suggest the eight dysregulated tRFs we uncovered here may be beneficially exploited as potential diagnostic biomarkers and/or therapeutic targets to treat age-related brain diseases.

SUBMITTER: Zhang S

PROVIDER: S-EPMC6914438 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain.

Zhang Shuai S Li Hejian H Zheng Ling L Li Hong H Feng Chengqiang C Zhang Wensheng W

Aging 20191120 22

Transfer RNA-derived fragments (tRFs) are known to contribute to multiple illnesses, including cancers, viral infections, and age-related neurodegeneration. In this study, we used senescence-accelerated mouse prone 8 (SAMP8) as a model of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, and a control, the senescence-accelerated mouse resistant 1 (SAMR1) model, to comprehensively explore differences in tRF expression between them. We discovered 570 tRF transcripts ...[more]

PMID: 31746776

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Project description:Background: Alzheimer's disease (AD) is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, several therapeutic approaches have shown unsatisfactory outcomes in the clinical setting. Thus, developing alternative therapies for the prevention and treatment of AD is critical. Salidroside (SAL) is critical, an herb-derived phenylpropanoid glycoside compound, has been shown to attenuate lipopolysaccharide (LPS)-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here, we show that SAL has a therapeutic effect in the senescence-accelerated mouse prone 8 (SAMP8) strain, a reliable and stable mouse model of AD. Methods: SAMP8 mice were treated with SAL, donepezil (DNP) or saline, and cognitive behavioral impairments were assessed using the Morris water maze (MWM), Y maze, and open field test (OFT). Fecal samples were collected and analyzed by 16S rRNA sequencing on an Illumina MiSeq system. Brain samples were analyzed to detect beta-amyloid (A?) 1-42 (A?1-42) deposition by immunohistochemistry (IHC) and western blotting. The activation of microglia and neuroinflammatory cytokines was detected by immunofluorescence (IF), western blotting and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel on a Luminex-MAGPIX multiplex immunoassay system. Results: Our results suggest that SAL effectively alleviated hippocampus-dependent memory impairment in the SAMP8 mice. SAL significantly 1) reduced toxic A?1-42 deposition; 2) reduced microglial activation and attenuated the levels of the proinflammatory factors IL-1?, IL-6, and TNF-? in the brain; 3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes and eliminated Clostridiales and Streptococcaceae, which may be associated with cognitive deficits); and 4) decreased the levels of proinflammatory cytokines, particularly IL-1?, IL-6, IL-17A and IL-12, in the peripheral circulation, as determined by a multiplex immunoassay. Conclusion: In summary, SAL reversed AD-related changes in SAMP8 mice, potentially by regulating the microbiota-gut-brain axis and modulating inflammation in both the peripheral circulation and central nervous system. Our results strongly suggest that SAL has a preventive effect on cognition-related changes in SAMP8 mice and highlight its value as a potential agent for drug development.

Dataset Information

Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain.

Publications

Identification of functional tRNA-derived fragments in senescence-accelerated mouse prone 8 brain.

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