Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex

Sánchez, Diego; Bajo‐Grañeras, Raquel; Caño-Espinel, Manuela del; García-Centeno, Rosa M.; García-Mateo, Nadia; Pascua-Maestro, Raquel; Ganfornina, Marı́a D.

doi:10.1016/j.exger.2015.04.003

Cited by 37 publications

(38 citation statements)

References 70 publications

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“…37 A possible role for SMIT in degenerative processes is currently under exploration. The constitutive SMIT levels in the brain 17 were found moderately increased in the hippocampus of aged mice; 38 however, severity of tissue damage was not related to SMIT expression in TgCRND8, a mouse model of Alzheimer's disease-like amyloid pathology. 39 …”

Section: Osmolyte Pathway Activation In Dmmentioning

confidence: 84%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control.

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Section: Osmolyte Pathway Activation In Dmmentioning

confidence: 84%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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“…We have previously analyzed ApoD expression in the nervous system under stress, damage or pathological conditions (Bajo‐Grañeras et al, ; Ganfornina et al, ; Ganfornina et al, ; Garcia‐Mateo et al, ; Li et al, ; Sanchez et al, ), and found that it is up‐regulated in glial cells in both CNS and PNS (reviewed by Dassati, Waldner, & Schweigreiter, ). In the healthy brain, the major cell type expressing ApoD is the mature oligodendrocyte (Supporting Information, Figure S1a and Ganfornina et al, ; Navarro, Del Valle, & Tolivia, ; Ong et al, ; Provost et al, ; Soreq et al, ), and the oligodendrocyte‐specific transcriptome is particularly altered in ApoD‐KO mice (Bajo‐Grañeras et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Various functional consequences derive from the ApoD‐KO “unfinished” myelin: (1) peripheral nerves decrease their conduction velocity by 40 weeks of age, without alterations in compound action potential amplitude or duration (Ganfornina et al, ) and (2) cerebellum‐dependent motor learning is compromised, without general locomotor deficits or alterations in other cognitive processes in the young adult (e.g., hippocampus‐dependent object recognition tasks, Sanchez et al, ). Cognitive and motor deficits do appear later upon further aging in ApoD‐KO (Ganfornina et al, ; Ganfornina et al, ; Sanchez et al, ), suggesting defective myelin vulnerability to age‐dependent deterioration.…”

Section: Discussionmentioning

confidence: 99%

Myelin extracellular leaflet compaction requires apolipoprotein D membrane management to optimize lysosomal‐dependent recycling and glycocalyx removal

García-Mateo

Pascua-Maestro

Pérez‐Castellanos

et al. 2017

Glia

Self Cite

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“…Protein of GPR45 functioned in the central nervous system, and was reported to be related to aging significantly [24]. Moreover, the marker with the greastest weight in tissue-specific models was expression of gene CORO6 in the Kidney renal clear cell model, which has been reported that to be regulated by age [25]. …”

Section: Resultsmentioning

confidence: 99%

Integrative analysis of methylation and transcriptional profiles to predict aging and construct aging specific cross-tissue networks

et al. 2016

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BackgroundAging is a complex process relating multi-scale omics data. Finding key age markers in normal tissues could help to provide reliable aging predictions in human. However, predicting age based on multi-omics data with both accuracy and informative biological function has not been performed systematically, thus relative cross-tissue analysis has not been investigated entirely, either.ResultsHere we have developed an improved prediction pipeline, the Integrating and Stepwise Age-Prediction (ISAP) method, to regress age and find key aging markers effectively. Furthermore, we have performed a serious of network analyses, such as the PPI network, cross-tissue networks and pathway interaction networks.ConclusionOur results find important coordinated aging patterns between different tissues. Both co-profiling and cross-pathway analyses identify more thorough functions of aging, and could help to find aging markers, pathways and relative aging disease researches.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0354-4) contains supplementary material, which is available to authorized users.

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Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex

Cited by 37 publications

References 70 publications

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Myelin extracellular leaflet compaction requires apolipoprotein D membrane management to optimize lysosomal‐dependent recycling and glycocalyx removal

Integrative analysis of methylation and transcriptional profiles to predict aging and construct aging specific cross-tissue networks

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