title: NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Neurosurgery Brain Repair, and Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, MDC-78, 12901 Bruce B Downs, Blvd, Tampa, FL, 33612, USA. Aflower4@health.usf.edu.
authors.forename: Antwoine
authors.initials: A
authors.lastname: Flowers
authors.affiliation: Department of Neurosurgery Brain Repair, and Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, MDC-78, 12901 Bruce B Downs, Blvd, Tampa, FL, 33612, USA. Jlee13@health.usf.edu.
authors.forename: Jea-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery Brain Repair, and Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, MDC-78, 12901 Bruce B Downs, Blvd, Tampa, FL, 33612, USA. sacosta@health.usf.edu.
authors.forename: Sandra
authors.initials: S
authors.lastname: Acosta
authors.affiliation: Research Service, James A Haley Veterans Hospital, Tampa, FL, USA. Chudson1@health.usf.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Hudson
authors.affiliation: School of Aging Studies, University of South Florida, 4202 E. Fowler Ave, Tampa, FL, 33620, USA. Bsmall@usf.edu.
authors.forename: Brent
authors.initials: B
authors.lastname: Small
authors.affiliation: Natura Therapeutics, Inc., Tampa, FL, USA. cds@naturatherapeutics.com.
authors.forename: Cyndy D
authors.initials: CD
authors.lastname: Sanberg
authors.affiliation: Department of Neurosurgery Brain Repair, and Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, MDC-78, 12901 Bruce B Downs, Blvd, Tampa, FL, 33612, USA. pbickfor@health.usf.edu.|Research Service, James A Haley Veterans Hospital, Tampa, FL, USA. pbickfor@health.usf.edu.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
mesh_terms: D000375:Aging; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002336:Carnosine / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology / Q000627:therapeutic use*; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007249:Inflammation / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D016207:Cytokines; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D051267:NF-E2-Related Factor 2; C522862:NT020 formula; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D051176:beta Catenin; D002762:Cholecalciferol; D002336:Carnosine