Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promo...Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.展开更多
Neurodegenerative diseases are becoming a big challenge for modern society.Neurodegenerative disorders strongly impact on patient and their caregivers.Moreover, since the population is becoming older, these pathologie...Neurodegenerative diseases are becoming a big challenge for modern society.Neurodegenerative disorders strongly impact on patient and their caregivers.Moreover, since the population is becoming older, these pathologies will deeply influence medical and socio-economic conditions in the next years.Therefore, efforts are needed to find new strategies devoted to define new protocols and identify novel substances able to prevent neurodegeneration or to improve the quality of life of people affected by neurodegenerative diseases(Alzheimer's Disease International, 2019).展开更多
The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,i.e.their capacity to fluctuate between different states of pluripotency,are not fully resolved.We developed and used a novel automation...The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,i.e.their capacity to fluctuate between different states of pluripotency,are not fully resolved.We developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(i.e.proliferation and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC metastability.Both compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent manner.Unlike EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to self-renew.Furthermore,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,respectively.Remarkably,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,respectively.All together,our data provide evidence that ESC metastability can be regulated at a metabolic level.展开更多
基金supported by Italian Ministry of Health ‘‘Ricerca Corrente”(to SF)
文摘Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.
基金supported by CNR project NUTRAGE (FOE-2019, DSB.AD004.271)by Ricerca corrente 2020 (to SF)。
文摘Neurodegenerative diseases are becoming a big challenge for modern society.Neurodegenerative disorders strongly impact on patient and their caregivers.Moreover, since the population is becoming older, these pathologies will deeply influence medical and socio-economic conditions in the next years.Therefore, efforts are needed to find new strategies devoted to define new protocols and identify novel substances able to prevent neurodegeneration or to improve the quality of life of people affected by neurodegenerative diseases(Alzheimer's Disease International, 2019).
基金This work was supported by Associazione Italiana Ricerca sul Cancro[IG-6128 to G.M.and IG-4840 to S.D.F.]Telethon[GGP-08120 to G.M.]+1 种基金Regione Campania-Programma Operativo Regionale[CRdC WP11 to S.F.,S.D.F,D.D.C.,G.M.and E.J.P.]Ministero Istruzione Universita Ricerca[Medical Research in Italy RBNE08HM7T_003 to E.J.P.].
文摘The molecular mechanisms controlling mouse embryonic stem cell(ESC)metastability,i.e.their capacity to fluctuate between different states of pluripotency,are not fully resolved.We developed and used a novel automation platform,the Cellmaker,to screen a library of metabolites on two ESC-based phenotypic assays(i.e.proliferation and colony phenotype)and identified two metabolically related amino acids,namely L-proline(L-Pro)and L-ornithine(L-Orn),as key regulators of ESC metastability.Both compounds,but mainly L-Pro,force ESCs toward a novel epiblast stem cell(EpiSC)-like state,in a dose-and time-dependent manner.Unlike EpiSCs,L-Pro-induced cells(PiCs)contribute to chimeric embryos and rely on leukemia inhibitor factor(LIF)to self-renew.Furthermore,PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF,respectively.Remarkably,PiC generation depends on both L-Pro metabolism(uptake and oxidation)and Fgf5 induction,and is strongly counteracted by antioxidants,mainly L-ascorbic acid(vitamin C,Vc).ESCs↔PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states,which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments,respectively.All together,our data provide evidence that ESC metastability can be regulated at a metabolic level.
