Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse

Currais, António; Farrokhi, Catherine; Dargusch, Richard; Armando, Aaron M.; Quehenberger, Oswald; Schubert, David; Maher, Pamela

doi:10.1093/gerona/glx104

Cited by 103 publications

(81 citation statements)

References 47 publications

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“…Memory impairments, especially episodic memory, occur as a consequence of normal aging across many species, including humans and rodents. Aged mice in different strains have significantly reduced spatial learning and memory abilities, and the onset of this age effect begins at middle age (even early adulthood) and persistently progresses onwards, such as SAMP8 and Kunming mice (Cao et al, , ; Chen et al, ; Currais et al, ). Bacterial infections during pregnancy result in a systemic inflammatory reaction in mothers and can affect cognition in their offspring.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer‐like behavioral and neuropathological changes in CD‐1 mice

et al. 2020

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Introduction Infections could contribute to Alzheimer's disease (AD) neuropathology in human. However, experimental evidence for a causal relationship between infections during the prenatal phase and the onset of AD is lacking. Methods CD‐1 mothers were intraperitoneally received lipopolysaccharide (LPS) with two doses (25 and 50 μg/kg) or normal saline every day during gestational days 15–17. A battery of behavioral tasks was used to assess the species‐typical behavior, sensorimotor capacity, anxiety, locomotor activity, recognition memory, and spatial learning and memory in 1‐, 6‐, 12‐, 18‐, and 22‐month‐old offspring mice. An immunohistochemical technology was performed to detect neuropathological indicators consisting of amyloid‐β (Aβ), phosphorylated tau (p‐tau), and glial fibrillary acidic protein (GFAP) in the hippocampus. Results Compared to the same‐aged controls, LPS‐treated offspring had similar behavioral abilities and the levels of Aβ42, p‐tau, and GFAP at 1 and 6 months old. From 12 months onward, LPS‐treated offspring gradually showed decreased species‐typical behavior, sensorimotor ability, locomotor activity, recognition memory, and spatial learning and memory, and increased anxieties and the levels of Aβ42, p‐tau, and GFAP relative to the same‐aged controls. Moreover, this damage effect (especially cognitive decline) persistently progressed onwards. The changes in these neuropathological indicators significantly correlated with impaired spatial learning and memory. Conclusions Prenatal exposure to low doses of LPS caused AD‐related features including behavioral and neuropathological changes from midlife to senectitude.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer‐like behavioral and neuropathological changes in CD‐1 mice

et al. 2020

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“…1, 2, and 3). Other natural CRMs, such as butein and fisetin (11,21,27,38,48,53,58,59), also inhibited T-cell activation (IC 50 = 2.8 μM and 5.2 μM, respectively) ( Figs. 1 and 3).…”

Section: Resultsmentioning

confidence: 94%

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

et al. 2019

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Caloric restriction (CR) is a major contributor to good health and longevity. CR mimetics (CRMs) are a group of plant-derived compounds capable of inducing the benefits of CR. Since a longevity gene, SIRT1, inhibits T-cell activation and SIRT1 loss results in increased T-cell activation, we hypothesized that compounds capable of activating SIRT1 signaling can inhibit T-cell activation and function as CRMs. Thus we propose, in the present study, the application of a T-cell activation-inhibitory assay to screen candidate CRMs. Well-known CRMs, such as resveratrol, butein, and fisetin, suppressed the anti-CD3/CD28 antibody-induced activation of mouse spleen T-cells. We next randomly assessed 68 plant-derived compounds for screening novel candidate CRMs using this bioassay and found that all four compounds showing IC 50 values <5 μM, such as curcumin, α-mangostin, nobiletin, and heptamethoxyflavone, have beneficial functions for health such as anti-inflammatory effect. These results suggest that the T-cell activation-inhibitory assay can be used to screen candidate CRMs.

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“…Tremendous studies have found that fisetin is effective in treatment of diabetic neuropathy, age-related neurodegenerative diseases and brain injury (Sandireddy et al, 2016;Chen et al, 2018;Currais et al, 2018). One important reason may be that fisetin has high brain uptake potential and BBB penetration (Maher, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Maher (2009) also found that fisetin exhibits high brain uptake potential. Fisetin can reduce cognitive deficits in old SAMP8 mice while improving impaired synaptic function, age-associated stress, and inflammation (Currais et al, 2018). However, the effect of fisetin on hyperglycemia-induced neurotoxicity has not been fully addressed.…”

Section: Introductionmentioning

confidence: 99%

Fisetin Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway

et al. 2020

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Hyperglycemia has been widely considered as a key risk factor for diabetic encephalopathy which can cause neuronal apoptosis and cognitive deficits. The flavonoid compound, fisetin, possesses potential neuroprotective effects and also enhances learning and memory. However, the role of fisetin in hyperglycemia-induced neuronal cytotoxicity has not been fully elucidated. In the present study, HT22 murine hippocampal neuronal cell line was used to establish the injured cell model. Cell proliferation and cytotoxicity assay, Hoechst 33258 staining, qRT-PCR, western blot analysis, and specific inhibitor were used to investigate the effect and molecular mechanisms of fisetin on high glucose (HG)-induced neurotoxicity in HT22 cells. Our results showed that 125 µM and 48 h of treatment was identified as optimal damage parameter of HG. Fisetin significantly improved HG-inhibited cell viability. The levels of LDH, malondialdehyde (MDA), and superoxide dismutase (SOD) were noticeably modulated by fisetin, which alleviated HG-induced HT22 cell oxidative damage. Besides, the apoptosis of HT22 cells was rescued by fisetin pretreatment. In addition, fisetin also prevented HG-induced downregulation of the mRNA expression of Bdnf, Gdnf, synaptophysin (Syp), and glutamate ionotropic receptor AMPA type subunit 1 (Gria1) in cells. More importantly, the decreased phosphorylation of phosphoinositide 3 kinase (PI3K), Akt, and cAMP-response element binding protein (CREB) was rescued by fisetin treatment and that neuroprotective effect of fisetin was partially blocked by PI3K inhibitor, LY294002. These findings indicate that fisetin has potent neuroprotective effect and prevents HG-induced neurotoxicity by activation of PI3K/Akt/CREB pathway.

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Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse

Cited by 103 publications

References 47 publications

Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer‐like behavioral and neuropathological changes in CD‐1 mice

Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer‐like behavioral and neuropathological changes in CD‐1 mice

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

Fisetin Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway

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