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NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats.
- Source :
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Journal of neuroinflammation [J Neuroinflammation] 2015 Sep 17; Vol. 12, pp. 174. Date of Electronic Publication: 2015 Sep 17. - Publication Year :
- 2015
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Abstract
- Background: Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells. Recent publications suggest that the age-related decline in the function of Wnt is a contributor to age-dependent decline in neural progenitors. Similarly, the aged neurogenic niche is characterized by higher levels of inflammatory cytokines. This increased inflammation contributes to the declining function of neural progenitor cells. NT-020, a proprietary blend of polyphenols, has been shown to increase proliferation of neural progenitors and improve cognitive function in aged rats.<br />Purpose and Methods: In this study, we examined the neurogenic niche in the subgranular zone of the dentate gyrus (SGZ) and the subventricular zone (SVZ) of young and aged rats to determine if dietary supplementation with NT-020 could regulate inflammation and oxidative stress response pathways in neurons, astrocytes, and microglia. Further, we examined NT-020's ability to modulate Wnt signaling in the aged neurogenic niche. To accomplish this, we utilized gene PCR arrays and immunohistochemistry.<br />Results: We observed an increase in nuclear localization of immunopositive labeling of β-catenin, HO-1, and Nrf2 in all subsets of cell types in both young and aged rats in the SGZ and SVZ following NT-020 treatment. NeuN-positive cells showed a basal increase in nuclear β-catenin in the aged rats, which was not observed in doublecortin (DCX)-labeled cells, microglia, or astrocytes. Reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated hippocampal tissue revealed that a significant percent of genes involved with inflammation are affected by treatment with NT-020. In addition, several genes that regulate Wnt activity were affected by supplementation.<br />Conclusions: The results suggest that NT-020 activates oxidative stress response pathways and supports pro-neurogenic gene expression in the hippocampus. This may represent the mechanism by which the NT-020 formula enhances performance in learning and memory tasks in aged mice.
- Subjects :
- Animals
Calcium-Binding Proteins genetics
Calcium-Binding Proteins metabolism
Carnosine pharmacology
Cell Proliferation drug effects
Cholecalciferol pharmacology
Computational Biology
Cytokines genetics
Cytokines metabolism
Dentate Gyrus cytology
Doublecortin Domain Proteins
Doublecortin Protein
Intercellular Signaling Peptides and Proteins metabolism
Male
Microfilament Proteins genetics
Microfilament Proteins metabolism
Microtubule-Associated Proteins metabolism
NF-E2-Related Factor 2 genetics
Nerve Tissue Proteins metabolism
Neurogenesis drug effects
Neuropeptides metabolism
Plant Extracts pharmacology
Rats
Rats, Inbred F344
Wnt Signaling Pathway drug effects
beta Catenin metabolism
Aging
Carnosine therapeutic use
Cholecalciferol therapeutic use
Inflammation drug therapy
NF-E2-Related Factor 2 metabolism
Plant Extracts therapeutic use
Wnt Signaling Pathway physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2094
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 26376629
- Full Text :
- https://doi.org/10.1186/s12974-015-0395-4