A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region...A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.展开更多
Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i....Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i.e., bioactive com- pounds obtained from Ecteinascidia turbinate to treat some types of cancer or rapamycin from Streptomyces hygroscop- icus to prevent organ rejection after transplant. This trend will continue simply due to the fact that Mother Nature has been synthesizing molecules for millions of years. In our lab- oratory, we have characterized several compounds obtained from natural sources and that possess important neuronal effects,展开更多
The development,maturation and regeneration of Schwann cells（SCs）,the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracel...The development,maturation and regeneration of Schwann cells（SCs）,the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracellular pathways.These regulatory molecules consist of integrins,neuregulins,growth factors,hormones,neurotransmitters,as well as entire intracellular pathways including protein-kinase A,C,Akt,Erk/MAPK,Hippo,mTOR,etc.For instance,Hippo pathway is overall involved in proliferation,apoptosis,regeneration and organ size control,being crucial in cancer proliferation process.In SCs,Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical challenges.Recently,among factors regulating SCs,also the signaling intermediates Src tyrosine kinase and focal adhesion kinase（FAK）proved relevant for SC fate,participating in the regulation of adhesion,motility,migration and in vitro myelination.In SCs,the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone,thus corroborating the importance of this steroid in the control of SC maturation.In this review,we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental,mature and regenerative states展开更多
We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To ide...We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.展开更多
Background:Cryoablation(CRYO)is a novel catheter ablation technique for atrial fibrillation(AF).However,un-certainty persists regarding the role of metabolic modifications associated with CRYO.This study was aimed at ...Background:Cryoablation(CRYO)is a novel catheter ablation technique for atrial fibrillation(AF).However,un-certainty persists regarding the role of metabolic modifications associated with CRYO.This study was aimed at explor-ing whether CRYO influences the metabolic signature–a possibility not previously investigated.Methods:Paired serum samples from patients with AF(n=10)were collected before and 24 h after CRYO.Untar-geted metabolomic analysis was conducted with LC-MS.Univariate and multivariate analyses were applied to identify differential metabolites between samples.Pathway enrichment and Pearson correlation analyses were performed to reveal the perturbed metabolic pathways and potential interactions.Results:Levels of 19 metabolites showed significant changes between baseline and 24 h after CRYO.Pathway analysis revealed that the perturbed metabolites were enriched in unsaturated fatty acid biosynthesis,retrograde en-docannabinoid signaling,and neuroactive ligand-receptor interactions.Pearson correlation analysis indicated strong correlations among differential metabolites,biochemical markers,and clinical indicators.Conclusions:CRYO induces systemic changes in the serum metabolome in patients with paroxysmal AF and pro-vides potential metabolic benefits.Our findings might enable enhanced understanding of the pathophysiology and metabolic mechanisms involved in catheter ablation.展开更多
Electric fishes(Gymnotiformes)inhabit Central and South America and form a relatively large group with more than 200 species.Besides a taxonomic challenge due to their still unresolved systematic,wide distribution and...Electric fishes(Gymnotiformes)inhabit Central and South America and form a relatively large group with more than 200 species.Besides a taxonomic challenge due to their still unresolved systematic,wide distribution and the variety of habitats they occupy,these fishes have been intensively studied due to their peculiar use of bioelectricity for electrolocation and communication.Conventional analysis of cells,tissues and organs have been complemented with the studies on the electric organ discharges of these fishes.This review compiles the results of 13 bioassays developed during the last 50 years,which used the quickness,low costs and functionality of the bioelectric data collection of Gymnotiformes to evaluate the effects of environmental contaminants and neuroactive drugs.展开更多
基金the Department of Pathophysiology of Hebei Medical University, China for their help
文摘A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.
文摘Despite the advances in combinatorial or synthetic chemis- try and bioinformatics, recent literature has demonstrated the relevance of nature and biomass as a source of new molecules to treat different pathologies, i.e., bioactive com- pounds obtained from Ecteinascidia turbinate to treat some types of cancer or rapamycin from Streptomyces hygroscop- icus to prevent organ rejection after transplant. This trend will continue simply due to the fact that Mother Nature has been synthesizing molecules for millions of years. In our lab- oratory, we have characterized several compounds obtained from natural sources and that possess important neuronal effects,
基金Financial support by University of Milan,institutional funding "Piano di sostegno per la ricerca 2016-Linea 2 Azione B"
文摘The development,maturation and regeneration of Schwann cells（SCs）,the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracellular pathways.These regulatory molecules consist of integrins,neuregulins,growth factors,hormones,neurotransmitters,as well as entire intracellular pathways including protein-kinase A,C,Akt,Erk/MAPK,Hippo,mTOR,etc.For instance,Hippo pathway is overall involved in proliferation,apoptosis,regeneration and organ size control,being crucial in cancer proliferation process.In SCs,Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical challenges.Recently,among factors regulating SCs,also the signaling intermediates Src tyrosine kinase and focal adhesion kinase（FAK）proved relevant for SC fate,participating in the regulation of adhesion,motility,migration and in vitro myelination.In SCs,the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone,thus corroborating the importance of this steroid in the control of SC maturation.In this review,we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental,mature and regenerative states
基金supported by a grant from National Key Basic Research Program of China(973 Program),No.2014CB542202a grant from Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)in China
文摘We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.
基金supported by grants from National Natural Science Foundation of China(82241057,82270532,81970287,82100530,and 82200556)the Foundation for Innovative Research Groups of Natural Science Foundation of Hubei Province,China(2021CFA010).
文摘Background:Cryoablation(CRYO)is a novel catheter ablation technique for atrial fibrillation(AF).However,un-certainty persists regarding the role of metabolic modifications associated with CRYO.This study was aimed at explor-ing whether CRYO influences the metabolic signature–a possibility not previously investigated.Methods:Paired serum samples from patients with AF(n=10)were collected before and 24 h after CRYO.Untar-geted metabolomic analysis was conducted with LC-MS.Univariate and multivariate analyses were applied to identify differential metabolites between samples.Pathway enrichment and Pearson correlation analyses were performed to reveal the perturbed metabolic pathways and potential interactions.Results:Levels of 19 metabolites showed significant changes between baseline and 24 h after CRYO.Pathway analysis revealed that the perturbed metabolites were enriched in unsaturated fatty acid biosynthesis,retrograde en-docannabinoid signaling,and neuroactive ligand-receptor interactions.Pearson correlation analysis indicated strong correlations among differential metabolites,biochemical markers,and clinical indicators.Conclusions:CRYO induces systemic changes in the serum metabolome in patients with paroxysmal AF and pro-vides potential metabolic benefits.Our findings might enable enhanced understanding of the pathophysiology and metabolic mechanisms involved in catheter ablation.
基金Supported by the Coordination of Improvement of Higher Education Personnel(CAPES),Ministry of Science,Technology and Innovation of Brazil(Grant No.PROAP/2014).
文摘Electric fishes(Gymnotiformes)inhabit Central and South America and form a relatively large group with more than 200 species.Besides a taxonomic challenge due to their still unresolved systematic,wide distribution and the variety of habitats they occupy,these fishes have been intensively studied due to their peculiar use of bioelectricity for electrolocation and communication.Conventional analysis of cells,tissues and organs have been complemented with the studies on the electric organ discharges of these fishes.This review compiles the results of 13 bioassays developed during the last 50 years,which used the quickness,low costs and functionality of the bioelectric data collection of Gymnotiformes to evaluate the effects of environmental contaminants and neuroactive drugs.
