Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells

2007 ◽  
Vol 16 (7) ◽  
pp. 697-705 ◽  
Author(s):  
Dwaine F. Emerich ◽  
Patricia Schneider ◽  
Briannan Bintz ◽  
Jebecka Hudak ◽  
Christopher G. Thanos
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Motor Function ◽  
Neuronal Loss ◽  
Rat Striatum ◽  
Control Group ◽  
Age Related ◽  
Alginate Capsules ◽  
And Function

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3–4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.

scholarly journals Dill Extract Induces Elastic Fiber Neosynthesis and Functional Improvement in the Ascending Aorta of Aged Mice with Reversal of Age-Dependent Cardiac Hypertrophy and Involvement of Lysyl Oxidase-Like-1

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 173 ◽  
Author(s):  
Wassim Fhayli ◽  
Quentin Boëté ◽  
Nadjib Kihal ◽  
Valérie Cenizo ◽  
Pascal Sommer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Ascending Aorta ◽  
Functional Improvement ◽  
Elastic Fibers ◽  
Aged Mice ◽  
Age Related ◽  
And Function

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase–like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10% v/v, in drinking water) on the structure and function of the ascending aorta. DE treatment, especially at 10%, of aged mice protected pre-existing elastic lamellae, reactivated tropoelastin and LOXL-1 expressions, induced elastic fiber neo-synthesis, and decreased the stiffness of the aging aortic wall, probably explaining the reversal of the age-related cardiac hypertrophy also observed following the treatment. DE could thus be considered as an anti-aging product for the cardiovascular system.

scholarly journals Porcine Choroid Plexus Epithelial Cells Induce Streptococcus suis Bacteriostasis In Vitro

2004 ◽  
Vol 72 (5) ◽  
pp. 3084-3087 ◽  
Author(s):  
Rüdiger A. Adam ◽  
Tobias Tenenbaum ◽  
Peter Valentin-Weigand ◽  
Maurice Laryea ◽  
Bernd Schwahn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Meningitis ◽  
Choroid Plexus ◽  
Host Defense ◽  
Streptococcus Suis ◽  
Active Role ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Choroid Plexus Epithelial

ABSTRACT The involvement of the choroid plexus in host defense during bacterial meningitis is unclear. Aiming to elucidate possible antibacterial mechanisms, we stimulated primary porcine choroid plexus epithelial cells (pCPEC) with proinflammatory cytokines and challenged them with various Streptococcus suis strains. In the supernatant of gamma interferon (IFN-γ)-stimulated pCPEC, streptococcal growth was markedly suppressed. Costimulation with tumor necrosis factor alpha enhanced this bacteriostatic effect, while supplementation of l-tryptophan completely eliminated it. We also demonstrate that an activation of indoleamine 2,3-dioxygenase in the pCPEC seems to be responsible for the IFN-γ-induced bacteriostasis. This supports the hypothesis of an active role of the choroid plexus in host defense against bacterial meningitis.

scholarly journals Increased Association of Deamidated αA-N101D with Lens Membrane of Transgenic αAN101D vs. Wild Type αA Mice: Potential Effects on Intracellular Ionic Imbalance and Membrane Disorganization

2020 ◽  
Author(s):  
Om Srivast ◽  
Kiran Srivast ◽  
Roy Joseph ◽  
Landon Wilson
Keyword(s):  
Epithelial Cells ◽  
Western Blot ◽  
Immunogold Labeling ◽  
Human Lens ◽  
Membrane Association ◽  
Related Protein ◽  
Wild Type ◽  
Age Related ◽  
Ionic Imbalance

Abstract We have generated two mouse models, in one by inserting the human lens αAN101D transgene in CRYαAN101D mice, and in the other by inserting human wild-type αA-transgene in CRYαAWT mice. The CRYαAN101D mice developed cortical cataract at about 7-months of age relative to CRYαAWT mice. The objective of the study was to determine the following relative changes in the lenses of CRYαAN101D- vs. CRYαAWT mice: age-related changes with specific emphasis on protein insolubilization, relative membrane-association of αAN101D vs. WTαA proteins, and changes in intracellular ionic imbalance and membrane organization. Methods: Lenses of varying ages from CRYαAWT and CRYαAN101D mice were compared for an age-related protein insolubilization. The relative lens membrane-association of the αAN101D- and WTαA proteins in the two types of mice was determined by immunohistochemical-, immunogold-labeling-, and western blot analyses. The relative levels of membrane-binding of recombinant αAN101D- and WTαA proteins was determined by an in vitro assay, and the levels of intracellular Ca2+ uptake and Na, K-ATPase mRNA were determined in the cultured epithelial cells from lenses of the two types of mice.Results: Compared to the lenses of CRYαAWT, the lenses of CRYαAN101D mice exhibited: (A) An increase in age-related protein insolubilization beginning at about 4-months of age. (B) A greater lens membrane-association of αAN101D- relative to WTαA protein during immunogold-labeling- and western blot analyses, including relatively a greater membrane swelling in the CRYαAN101D lenses. (C) During in vitro assay, the greater levels of binding αAN101D- relative to WTαA protein to membranes was observed. (D) The 75% lower level of Na, K-ATPase mRNA but 1.5X greater Ca2+ uptake were observed in cultured lens epithelial cells of CRYαAN101D- than those of CRYαAWT mice. Conclusions: The results show that an increased lens membrane association of αAN101D--relative WTαA protein in CRYαAN101D mice than CRYαAWT mice occurs, which causes intracellular ionic imbalance, and in turn, membrane swelling that potentially leads to cortical opacity.

scholarly journals Metformin protects lens epithelial cells against senescence in a naturally aged mouse model

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Mengmeng Chen ◽  
Yushan Fu ◽  
Xu Wang ◽  
Ruitong Wu ◽  
Dongmei Su ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Vision Loss ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Ageing Process ◽  
Lens Epithelial Cells ◽  
Control Group ◽  
Aged Mouse ◽  
Ampk Pathway ◽  
Age Related

AbstractThe senescence of lens epithelial cells (LECs) is a major factor leading to age-related cataract (ARC). ARC results in visual impairment and severe vision loss in elderly patients. However, the specific mechanism of ARC remains unclear, and there are no effective therapeutic agents to halt the formation of ARC. This study aimed to assess the underlying mechanism of the formation of ARC and investigate the potential anti-ageing effect of metformin (MET) on ARC. Male C57BL/6 mice were divided into three groups: the control group having young mice (3 months old, n = 40), the naturally aged group (aged 20 months, n = 60) and the MET group (MET, 20 months, n = 60). Mice in the control and the naturally aged groups were fed a standard purified mouse diet ad libitum and water, whereas those in the MET group were fed chows supplemented with 0.1% MET for 10 months. The transparency of the lens and age-associated proteins p21 and p53 were analysed in the LECs of these three groups. Furthermore, we determined the expressions of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway and the effect of MET on this pathway in LECs during the ageing process of ARC. In addition, the relationship between autophagy and the senescence of LECs and the role of MET in the autophagy of LECs during the ageing process of ARC were examined. Our results indicated that age-related inactivation of the AMPK pathway and impairment of autophagy might contribute to the senescence of LECs and the occurrence of ARC. More importantly, these results demonstrated that MET effectively alleviated the senescence of LECs and the formation of ARC probably via inactivation of the AMPK pathway and augmentation of autophagy. These findings revealed that MET can be exploited as a potentially useful drug for ARC prevention. Our study will help in enlightening the development of innovative strategies for the clinical treatment of ARC.

scholarly journals Ultrastructure changes and expression of NLRP3 inflammasome  in lens anterior capsule of patient with cataracts associated with uveitis

2019 ◽  
Author(s):  
Chu Zhang ◽  
Chong-Hui Ying ◽  
siqin Sun ◽  
yuechun Wen ◽  
Zicheng Zhu
Keyword(s):  
Epithelial Cells ◽  
Ultrastructural Changes ◽  
Lens Epithelial Cells ◽  
Control Group ◽  
Anterior Capsule ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Age Related ◽  
The Difference ◽  
Domain 3

Abstract ● AIM : T o investigate the expression of nod-like receptor pyrin domain 3 (NLRP3) in lens anterior capsule of Uveitis associated with cataract and observe the ultrastructural changes of them . ● Methods: 17(22 eyes) cases of uveitis associated with cataract were selected a s experimental group and 1 0 (18 eyes) cases of age-related cataract were selected a s contro l group. The expressions of NLRP3, apoptosis-related speckle protein （ASC） and caspase-1 protein were tested by immunohistochemical and the ultrastructural changes of anterior capsul e was observed under electron microscope. ● Results: The expression of NLRP3 、 caspase-1 and ASC in the anterior capsu le of cataracts associated with uveitis was significantly higher than that of the control group, the difference was statistically significant (p ＜ 0.05). The apoptotic changes of lens epithelial cells in uveitis associated with cataract were obvious, and the apoptotic changes of lens epithelial cells were mild in age-related cataract patients. ● Conclusion: Strongly postive expressed NLRP3 inflamma some and obvious apoptotic changes are founded in the lens epithelial cells of patients with uveitis associat ed with cataract, suggesting that NLRP3 inflamma some and the apoptosis of lens epithelial cells may play a role in the progress of uveitis associat ed with cataract.

scholarly journals A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexa N. Lauer ◽  
Rene Scholtysik ◽  
Andreas Beineke ◽  
Christoph Georg Baums ◽  
Kristin Klose ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Choroid Plexus ◽  
Cellular Proliferation ◽  
Inflammatory Responses ◽  
Streptococcus Suis ◽  
Gene Set Enrichment Analysis ◽  
Rna Seq

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.

The CCL7-CCL2-CCR2 Axis Regulates Age-Related Alterations in ADSCs 

2021 ◽  
Author(s):  
Keya Li ◽  
Guiying Shi ◽  
Xuepei Lei ◽  
Yiying Huang ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Autologous Transplantation ◽  
Hippo Signaling ◽  
Related Disorder ◽  
Promising Strategy ◽  
Age Related ◽  
Minimum Number ◽  
And Function ◽  
The Relationship ◽  
Harmful Effects

Abstract Background and ObjectivesAdipose-tissue derived stem cells (ADSCs) autologous transplantation have been a promising strategy for aging-related disorder. But the relationship between ADSCs senescence and organismal aging were still no consistent conclusions. Toward this end, we analyzed the senescence properties of ADSCs from different age donors to furthermore understand the differences of cells between young and senile donors and verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation.Methods and ResultsWe detected the characteristics, function, gene expression, apoptosis, cell cycle, SA-β-gal staining, and transcription features of ADSCs from 1-month mice and 20-month mice. ADSCs from old donors had some senescence-associated changes with less ability to proliferation than ADSCs from 1-month mice. Differentiation ability, cell surface markers, and SA-β-Gal staining did not differ across donor age, while cells exhibit a more remarkable age-related changes through continuous passages. According to the results of transcriptome analysis, the CCL7-CCL2-CCR2 axis and Hippo signaling pathway would be considered as its possible mechanisms. ConclusionsOur study reveals that ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 which lies behind this change would be a potential target for gene therapy to reduce harmful effects of ADSCs from old donors. To make autologous transplantation work better, we would recommend that ADSCs should be cryopreserved in youth with minimum number of passages.

scholarly journals In Vitro Study on the Regulation of Annexin IV and VEGF by hCG in the Human Endometrium

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shaoyuan Xu ◽  
Jie Li ◽  
Xiaoyan Chen ◽  
Beiyu Liu
Keyword(s):  
Epithelial Cells ◽  
In Vitro Study ◽  
Control Group ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Endometrial Cells ◽  
Mrna And Protein Expression ◽  
Endothelial Growth Factor ◽  
Annexin Iv

Objective. Whether changes in vascular endothelial growth factor (VEGF) and annexin IV during implantation are regulated through the LH/hCG-R needs further research. To investigate the mechanism of hCG on the expression of annexin IV and VEGF in human endometrial cells. Methods. Endometrial cells were isolated and identified from human specimens. The proportion of glandular and epithelial cells was analyzed. Annexin IV and VEGF were analyzed by qRT-PCR (mRNA), western blot (proteins), and immunohistochemistry (proteins). Protein location was identified by immunohistochemistry. The cells were cultured with hCG, hCG/PD98059 (a MAPK inhibitor), or no treatment (control). Results. The proportions between the glandular epithelial cells and stromal cells at inoculation and when adding hCG were 25.8 ± 0.2% and 27.8 ± 0.04%, respectively ( P > 0.05 ). LH/hCG-R, annexin IV, and VEGF were found in the cytoplasm of endometrial cells. After 2, 6, 12, and 24 h of hCG treatment, compared with 1 h, VEGF mRNA was increased by 1.25-fold, 3.19-fold, 4.21-fold, and 4.86-fold and annexin IV by 2.23-fold, 3.37-fold, 5.14-fold, and 5.02-fold. Compared with the control group, annexin IV mRNA and protein were increased in the hCG and hCG/PD98059 groups (mRNA/protein: 1.99-fold/1.80-fold and 2.33-fold/1.93-fold, P < 0.05 ). Compared with the control group, VEGF mRNA and protein were increased in the hCG group (mRNA/protein: 2.30-fold/1.86-fold), but not in the hCG/PD98059 group. Conclusion. hCG could upregulate the mRNA and protein expression of annexin IV and VEGF. The upregulation of annexin IV by hCG could not be inhibited by PD98059, but the upregulation of VEGF by hCG could.

A Comparative Study of Preparation Techniques for Improving the Viability of Striatal Grafts Using Vital Stains, in Vitro Cultures, and in Vivo Grafts

1996 ◽  
Vol 5 (6) ◽  
pp. 599-611 ◽  
Author(s):  
Rosemary A. Fricker ◽  
Roger A. Barker ◽  
James W. Fawcett ◽  
Stephen B. Dunnett
Keyword(s):  
Cell Survival ◽  
Cell Suspension ◽  
Single Cells ◽  
Rat Striatum ◽  
Adult Rat ◽  
Striatal Grafts ◽  
Vital Stains ◽  
And Function

Cell suspension grafts from embryonic striatal primordia placed into the adult rat striatum survive well and are able to alleviate a number of behavioral deficits caused by excitotoxic lesions to this structure. However, neither the anatomical connectivity between the graft and host nor the functional recovery elicited by the grafts is completely restored. One way in which the survival and function of embryonic striatal grafts may be enhanced is by the improvement of techniques for the preparation of the cell suspension prior to implantation, an issue that has been addressed only to a limited extent. We have evaluated a number of parameters during the preparation procedure, looking at the effects on cell survival over the first 24 h from preparation using vital dyes and the numbers of surviving neurons in vitro, after 4 days in culture, in addition to graft survival and function in vivo. Factors influencing cell survival include the type of trypsinization procedure and the age of donor tissues used for suspension preparation. The presence of DNase has no effect on cell viability but aids the dissociation of the tissue to form single cells. These results have important implications for the use of embryonic striatal grafts in animal models of Huntington's disease, and in any future clinical application of this research.

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