Dataset Information

Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

ABSTRACT: D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.

SUBMITTER: Zhou YY

PROVIDER: S-EPMC4503422 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

Zhou Yue-Yue YY Ji Xiong-Fei XF Fu Jian-Ping JP Zhu Xiao-Juan XJ Li Rong-Hua RH Mu Chang-Kao CK Wang Chun-Lin CL Song Wei-Wei WW

PloS one 20150715 7

D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chrom ...[more]

PMID: 26176541

Similar Datasets

Project description:Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

Project description:BackgroundAging is closely associated to several deleterious conditions and cognitive impairment. Administration of low-dose paracetamol (APAP) has previously been reported to improve cognitive performance in both human and animal studies. However, the altered cognitive effects of low-dose APAP treatment in the aging brain have not been elucidated.ObjectivesThe purpose of this study was to determine whether low-dose APAP treatment improves cognitive dysfunction in a d-galactose (d-gal)-induced aging model.Materials and methodsAPAP (15 and 50 mg/kg p.o.) and vitamin E (Vit E 100 mg/kg p.o.) were administered once daily to d-gal-injected mice (200 mg/kg s.c.) for 6 weeks. The elevated plus maze (EPM), open field, novel object recognition (NOR), and Morris water maze (MWM) tests, respectively, were used to measure altered neurobehavioral functions, including anxiety-like behavior and exploratory locomotor activity, as well as learning and memory performance. The gene transcription of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling in brain tissues was evaluated by real-time polymerase chain reaction.ResultsCompared to the control, d-gal significantly decreased exploratory locomotor activity and NOR and MWM performance but did not significantly change the activity in the EPM test. However, APAP50 and Vit E significantly reversed the effects of d-gal injection on exploratory locomotor activity. In addition, low-dose APAP (15 and 50 mg/kg) and Vit E significantly improved the reduction in NOR and MWM performance induced by d-gal. Real-time polymerase chain reaction analysis revealed that the mRNA expression of BDNF, neurotrophic tyrosine receptor kinase (NTRK), which is the gene coding TrkB receptor, and cAMP response element-binding protein (CREB) was significantly decreased in the frontal cortex and hippocampus of the d-gal mice. However, APAP50 and Vit E significantly increased BDNF and NTRK mRNA expression in both the frontal cortex and the hippocampus. A lower dose of APAP (15 mg/kg) significantly elevated the mRNA expression of NTRK, but only in the hippocampus. Moreover, APAP50 significantly increased CREB mRNA expression in the frontal cortex and hippocampus.ConclusionLow-dose APAP treatment has a neuroprotective effect on cognitive dysfunction in the d-gal aging model, and the underlying molecular mechanisms depend on the activation of BDNF/TrkB signaling.

Dataset Information

Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

Publications

Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets