Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice

Wang, Jiao; Li, Qian; Kong, Yanyan; Zhou, Fangfang; Li, Jie; Li, Weihao; Wang, Kai; Wu, Ting; Guan, Yihui; Xie, Jing; Wen, Tao

doi:10.3389/fnagi.2017.00393

Cited by 3 publications

(3 citation statements)

References 70 publications

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“…The 860 DEGs were analyzed using the functional annotation tool DAVID Bioinformatics Resources (2021 Update). Age-regulated DEGs and their main functions were in agreement with previous results [ 41 , 42 , 43 ] and external publications [ 44 , 45 ] and identified immune process and transcriptional regulations, inflammation, and cytokine production as regulators in brain aging. Consistent with this, marker genes indicative of activated astrocytes and microglial cells were found to be more highly expressed in the old brain [ 39 , 46 ].…”

Section: Discussionsupporting

confidence: 91%

“…Li and colleagues identified 1054 DEGs in the hippocampus of 24- vs. 2-month-old male C57BL/6J mice that are closely related to neuroinflammation and involved in the regulation of immune processes, confirming our analysis [ 35 ]. Wang and colleagues analyzed the intersection of 139 up-regulated genes in the hippocampus of 24- and 29-month-old male C57BL/6 mice compared with 3-month-old mice and detected similar processes to our analysis: immune system process, innate immune response, defense response to viruses, and inflammatory response [ 44 ]. A cell type-specific analysis in the hippocampus is certainly worthwhile, as such an analysis in the whole brain has shown that aging triggers specific transcriptional processes in different cell types and that individual genes can be oppositely regulated between different cell types [ 47 ].…”

Section: Discussionmentioning

confidence: 65%

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Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

Schmidt

Haase

Best

et al. 2022

Cells

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Cognitive decline is one of the greatest health threats of old age and the maintenance of optimal brain function across a lifespan remains a big challenge. The hippocampus is considered particularly vulnerable but there is cross-species consensus that its functional integrity benefits from the early and continuous exercise of demanding physical, social and mental activities, also referred to as environmental enrichment (EE). Here, we investigated the extent to which late-onset EE can improve the already-impaired cognitive abilities of lifelong deprived C57BL/6 mice and how it affects gene expression in the hippocampus. To this end, 5- and 24-month-old mice housed in standard cages (5mSC and 24mSC) and 24-month-old mice exposed to EE in the last 2 months of their life (24mEE) were subjected to a Barnes maze task followed by next-generation RNA sequencing of the hippocampal tissue. Our analyses showed that late-onset EE was able to restore deficits in spatial learning and short-term memory in 24-month-old mice. These positive cognitive effects were reflected by specific changes in the hippocampal transcriptome, where late-onset EE affected transcription much more than age (24mSC vs. 24mEE: 1311 DEGs, 24mSC vs. 5mSC: 860 DEGs). Remarkably, a small intersection of 72 age-related DEGs was counter-regulated by late-onset EE. Of these, Bcl3, Cttnbp2, Diexf, Esr2, Grb10, Il4ra, Inhba, Rras2, Rps6ka1 and Socs3 appear to be particularly relevant as key regulators involved in dendritic spine plasticity and in age-relevant molecular signaling cascades mediating senescence, insulin resistance, apoptosis and tissue regeneration. In summary, our observations suggest that the brains of aged mice in standard cage housing preserve a considerable degree of plasticity. Switching them to EE proved to be a promising and non-pharmacological intervention against cognitive decline.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 65%

Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

Schmidt

Haase

Best

et al. 2022

Cells

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“…14-3-3ζ is a key regulator that mediates signal transduction by binding to phosphoserine-containing proteins during the hippocampal aging process 28. Upregulation of 14-3-3ζ helps to promote hippocampal development 29. Moreover, 14-3-3ζ is potentially a regulator with a similar function to that of β-catenin, which is a central effector of Wnt signaling in metastasis.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Study of a Parkinson's Disease Model of Undifferentiated SH-SY5Y Cells Induced by a Proteasome Inhibitor

Jiang¹,

Yu²,

Liu³

et al. 2019

Int. J. Med. Sci.

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Parkinson's disease (PD) is one of the most common nervous system degenerative diseases. However, the etiology of this disease remains elusive. Here, a proteasome inhibitor (PSI)-induced undifferentiated SH-SY5Y PD model was established to analyze protein alterations through proteomic study. Methods: Cultured undifferentiated SH-SY5Y cells were divided into a control group and a group treated with 2.5 µM PSI (PSI-treated group). An methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell viability. Acridine orange/ethidium bromide (AO/EB), α-synuclein immunofluorescence and hematoxylin and eosin (H&E) staining were applied to evaluate apoptosis and cytoplasmic inclusions, respectively. The protein spots that were significantly changed were separated, analyzed by 2D gel electrophoresis and DIGE De Cyder software, and subsequently identified by MALDI-TOF mass spectrometry and database searching. Results: The results of the MTT assay showed that there was a time and dose dependent change in cell viability following incubation with PSI. After 24 h incubation, PSI resulted in early apoptosis, and cytoplasmic inclusions were found in the PSI-treated group through H&E staining and α-synuclein immunofluorescence. Thus, undifferentiated SH-SY5Y cells could be used as PD model following PSI-induced inhibition of proteasomal function. In total, 18 proteins were differentially expressed between the groups, 7 of which were up-regulated and 11 of which were down-regulated. Among them, 5 protein spots were identified as being involved in the ubiquitin proteasome pathway-induced PD process. Conclusions: Mitochondrial heat shock protein 75 (MTHSP75), phosphoglycerate dehydrogenase (PHGDH), laminin binding protein (LBP), tyrosine 3/tryptophan 5-monooxygenase activation protein (14-3-3ε) and YWHAZ protein (14-3-3ζ) are involved in mitochondrial dysfunction, serine synthesis, amyloid clearance, apoptosis process and neuroprotection. These findings may provide new clues to deepen our understanding of PD pathogenesis.

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Synergistic gene regulation by thyroid hormone and glucocorticoid in the hippocampus

Espina

Bagamasbad

2022

Vitamins and Hormones

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Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice

Cited by 3 publications

References 70 publications

Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

Proteomic Study of a Parkinson's Disease Model of Undifferentiated SH-SY5Y Cells Induced by a Proteasome Inhibitor

Synergistic gene regulation by thyroid hormone and glucocorticoid in the hippocampus

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