S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation

Zhang, Yawen; Ma, Rui; Deng, Qian; Wang, Wencheng; Cao, Chi; Yu, Chunyang; Li, Shulin; Shi, Lei; Tian, Jiang

doi:10.1016/j.jchemneu.2023.102232

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…Excessive predominance of pathological species Lachnoclostridium in the gut microbiota can increase the production of inflammatory mediators accelerating the aging process ( Manchia et al, 2023 ). In addition, research has suggested that S-adenosylmethionine ameliorates cognitive impairment in brain aging by inhibiting oxidative stress and neuroinflammation ( Zhang et al, 2023b ). Spermidine impedes brain aging by inducing autophagy, preventing apoptosis, and reducing the accumulation of inflammation ( Xu et al, 2020 ; Yang et al, 2020 ; Wortha et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach

Lin,

Tang,

Liu

et al. 2024

Front. Pharmacol.

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Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage.Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics.Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging.Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.

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Section: Discussionmentioning

confidence: 99%

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach

Lin,

Tang,

Liu

et al. 2024

Front. Pharmacol.

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“…On the other hand, it was recently demonstrated that S-adenosil-L-metionina (SAM) treatment was able to reverse cognitive impairment and depression-like behaviors in an animal model of brain aging with D-galactose. In those animals, it was observed the reduction of neuronal cell death, increasing the level of neurotrophic factor derived from the brain in the hippocampus, as well as reducing the levels of pro-in ammatory factors in the hippocampus and serum [20]. Thus, considering that the protective properties of caffeine have long been explored in murine models and the activation of the NLRP3 in ammasome appears to be a central event in mediating the deleterious effects of in ammation in the central nervous system, in this study, we investigated whether the neuroprotective effects of caffeine are mediated by the transcriptional inhibition of the Nrf2/Txn1/Nlrp3 axis in the hippocampus of mice exposed to LPS.…”

Section: Introductionmentioning

confidence: 94%

Methyl group donor reduces the Caffeine hippocampal anti-inflammatory effects and potentiates the LPS effect by positive transcription of the Nrf2/Txn1/Nlrp3 axis

Coque,

Sanna,

Carvalho

et al. 2024

Preprint

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Nrlp3 inflammasome activation is closely related to the Nrf2/Txn1/Nlrp3 axis, since nod-like receptor 3 (NLRP3) has a critical role through interaction with thioredoxin-interacting protein (TXNIP), which upon dissociating from the Trx1/TXNIP complex and interacting with Nrlp3, promotes the activation of the complex. In this context, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role and can inhibit the activation of the inflammasome. Therefore, the objective of this study was to investigate in inflammatory conditions induced by LPS in vivo and in vitro whether the neuroprotective effect of caffeine would be mediated by the Nrf2/Txn1/Nlrp3 axis. Here, we demonstrate using an in vivo model of neuroinflammation induced by i.p. injection of LPS (0.33 mg/kg) that the reduction in Nrf2 expression and the increase in Nrlp3 and Txn1 expression promoted by LPS were significantly prevented and/or reversed by pre-treatment with caffeine without a direct involvement of epigenetic mechanisms. Furthermore, in vitro results revealed a pro-inflammatory effect for treatment with the CH3 donor (SAM) and an anti-inflammatory effect for the Dnmt inhibitor, RG108. Thus, the joint analysis of the results allows us to conclude that the neuroprotective effect of caffeine observed by the negative modulation of the pro-inflammatory genes, Nlrp3/Txn1, and positive modulation of Nfr2, may be mediated by underlying molecular mechanisms sensitive to positive modulation and/or or negative activation of DNMTs enzymes. We emphasize that additional studies are needed to elucidate the involvement of DNMTs in caffeine-mediated neuroprotection.

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“…In addition, in a rodent model of galactose-induced brain aging, Zhang et al [64] showed that chronic treatment with SAMe enhanced antioxidant capacity and reduced the expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) genes in the hippocampus, and improved cognitive impairment in rat behavior [64].…”

Section: Genesmentioning

confidence: 99%

Prenatal SAMe Treatment Changes via Epigenetic Mechanism/s USVs in Young Mice and Hippocampal Monoamines Turnover at Adulthood in a Mouse Model of Social Hierarchy and Depression

Becker

Gorobets

Shmerkin

et al. 2023

IJMS

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The role of hippocampal monoamines and their related genes in the etiology and pathogenesis of depression-like behavior, particularly in impaired sociability traits and the meaning of changes in USVs emitted by pups, remains unknown. We assessed the effects of prenatal administration of S-adenosyl-methionine (SAMe) in Sub mice that exhibit depressive-like behavior on serotonergic, dopaminergic and noradrenergic metabolism and the activity of related genes in the hippocampus (HPC) in adulthood in comparison to saline-treated control Sub mice. During postnatal days 4 and 8, we recorded and analyzed the stress-induced USVs emitted by the pups and tried to understand how the changes in the USVs’ calls may be related to the changes in the monoamines and the activity of related genes. The recordings of the USVs showed that SAMe induced a reduction in the emitted flat and one-frequency step-up call numbers in PND4 pups, whereas step-down type calls were significantly increased by SAMe in PND8 pups. The reduction in the number of calls induced by SAMe following separation from the mothers implies a reduction in anxiety, which is an additional sign of decreased depressive-like behavior. Prenatal SAMe increased the concentrations of serotonin in the HPC in both male and female mice without any change in the levels of 5HIAA. It also decreased the level of the dopamine metabolite DOPAC in females. There were no changes in the levels of norepinephrine and metabolites. Several changes in the expression of genes associated with monoamine metabolism were also induced by prenatal SAMe. The molecular and biochemical data obtained from the HPC studies are generally in accordance with our previously obtained data from the prefrontal cortex of similarly treated Sub mice on postnatal day 90. The changes in both monoamines and their gene expression observed 2–3 months after SAMe treatment are associated with the previously recorded behavioral improvement and seem to demonstrate that SAMe is effective via an epigenetic mechanism.

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S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation

Cited by 11 publications

References 48 publications

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach

Methyl group donor reduces the Caffeine hippocampal anti-inflammatory effects and potentiates the LPS effect by positive transcription of the Nrf2/Txn1/Nlrp3 axis

Prenatal SAMe Treatment Changes via Epigenetic Mechanism/s USVs in Young Mice and Hippocampal Monoamines Turnover at Adulthood in a Mouse Model of Social Hierarchy and Depression

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