A unique combination of micronutrients rejuvenates cognitive performance in aged mice

Perez, Sam D.; Du, Kristy; Rendeiro, Catarina; Wang, Lin; Wu, Qian; Rubakhin, Stanislav S.; Vazhappilly, Rema; Baxter, Jeffrey H.; Sweedler, Jonathan V.; Rhodes, Justin S.

doi:10.1016/j.bbr.2016.11.019

Cited by 11 publications

(7 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For each protein (doublecortin, S100β, collagen IV), a one-in-six series of sections (240 μm) increments separating each section) through the dentate gyrus of the hippocampus were analyzed. To assess immature neuron quantity (doublecortin + ; DCX + ), free-floating sections were washed in PBS and treated with a solution of 0.3% Triton-X and 6% normal donkey serum (NDS) in PBS (PBS-X plus 6% NDS) for 60 min [Perez et al, 2016]. Sections were then incubated in a PBS-X plus 6% NDS solution with primary antibody goat anti-DCX (1:1000, Santa Cruz Biotechnology) for 48 hrh at 4 °C.…”

Section: Brain Iimmunohistochemistrymentioning

confidence: 99%

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle

Huntsman

Rendeiro

Merritt

et al. 2018

Experimental Gerontology

Self Cite

View full text Add to dashboard Cite

Perivascular stromal cells, including mesenchymal stem/stromal cells (MSCs), secrete paracrine factor in response to exercise training that can facilitate improvements in muscle remodeling. This study was designed to test the capacity for muscle-resident MSCs (mMSCs) isolated from young mice to release regenerative proteins in response to mechanical strain in vitro, and subsequently determine the extent to which strain-stimulated mMSCs can enhance skeletal muscle and cognitive performance in a mouse model of uncomplicated aging. Protein arrays confirmed a robust increase in protein release at 24h following an acute bout of mechanical strain in vitro (10%, 1Hz, 5h) compared to non-strain controls. Aged (24month old), C57BL/6 mice were provided bilateral intramuscular injection of saline, non-strain control mMSCs, or mMSCs subjected to a single bout of mechanical strain in vitro (4×10). No significant changes were observed in muscle weight, myofiber size, maximal force, or satellite cell quantity at 1 or 4wks between groups. Peripheral perfusion was significantly increased in muscle at 4wks post-mMSC injection (p<0.05), yet no difference was noted between control and preconditioned mMSCs. Intramuscular injection of preconditioned mMSCs increased the number of new neurons and astrocytes in the dentate gyrus of the hippocampus compared to both control groups (p<0.05), with a trend toward an increase in water maze performance noted (p=0.07). Results from this study demonstrate that acute injection of exogenously stimulated muscle-resident stromal cells do not robustly impact aged muscle structure and function, yet increase the survival of new neurons in the hippocampus.

show abstract

Section: Brain Iimmunohistochemistrymentioning

confidence: 99%

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle

Huntsman

Rendeiro

Merritt

et al. 2018

Experimental Gerontology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pathway analyses suggest that age-related changes in inflammation- and immune-related gene expression may be more pronounced in the hippocampus compared to other brain regions and more pronounced in females versus males [ 7 , 8 ]. Indeed, we noted that studies employing female subjects alone or in combination with male subjects routinely report higher basal IL-6 mRNA or protein expression in old vs. young brains [ 8 , 34 , 38 , 39 ]; whereas, only a subset of studies employing male subjects alone report this age-related increase in basal expression (increased mRNA: [ 36 ]; increased protein: [ 21 , 33 , 40 – 42 ]; no change mRNA: [ 11 , 12 , 35 , 43 ]; no change protein: [ 22 , 23 , 37 ]). As such, we sought to clarify how pro-inflammatory (IL-1α, IL-1β, IL-2, IL-3, IL-5 IL-6—see discussion, IL-9, IL-12p40, IL-12p70, IL-17, eotaxin, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, TNFα, MCP-1, or GM-CSF) and anti-inflammatory cytokine expression (IL-4, IL-10, IL-13, G-CSF) may change with age by studying multiple cytokines across multiple brain regions of both male and female subjects, using 2 strains of mice bred in-house as well as rats obtained from the NIA aging colony.…”

Section: Introductionmentioning

confidence: 99%

Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions

Porcher

Bruckmeier

Burbano

et al. 2021

J Neuroinflammation

View full text Add to dashboard Cite

Background Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound—particularly for interleukin 6 (IL-6)—possibly due to differences in sex, species/strain, and/or the brain regions studied. Methods As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate. Results In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1β in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1β. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments. Conclusions Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined.

show abstract

“…This may contribute to the increased expression of IL-6 in aged mouse brains. In contrast, Petez et al [ 33 ] observed slightly increased IL-10 expression in the aged (18-month-old) hippocampus relative to the adult (4-month-old) hippocampus in C57BL/6 mice. Other groups have also demonstrated that activated microglia from aged mice showed higher levels of IL-10 than activated microglia from adult mice [ 34 ].…”

Section: Discussionmentioning

confidence: 87%

Dendropanax morbiferaLéveille extract ameliorates D-galactose-induced memory deficits by decreasing inflammatory responses in the hippocampus

et al. 2017

View full text Add to dashboard Cite

In the present study, we examined the effects of Dendropanax morbifera Léveille leaf extract (DML) on D-galactose-induced morphological changes in microglia and cytokines, including pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Administration of DML to D-galactose-treated mice significantly improved D-galactose-induced reduction in escape latency, swimming speed, and spatial preference for the target quadrant. In addition, administration of DML to D-galactose-treated mice significantly ameliorated the microglial activation and increases of IL-1β, IL-6, and TNF-α levels in the hippocampus. Administration of D-galactose significantly reduced IL-4 levels in the hippocampus, while administration of DML to D-galactose-treated mice significantly increased IL-4 level. However, we did not observe any significant changes in IL-10 levels in hippocampal homogenates. These results suggest that DML reduces D-galactose-induced mouse senescence by reducing pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, as well as increasing anti-inflammatory cytokine IL-4.

show abstract

A unique combination of micronutrients rejuvenates cognitive performance in aged mice

Cited by 11 publications

References 125 publications

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle

The impact of mechanically stimulated muscle-derived stromal cells on aged skeletal muscle

Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions

Dendropanax morbiferaLéveille extract ameliorates D-galactose-induced memory deficits by decreasing inflammatory responses in the hippocampus

Contact Info

Product

Resources

About