It consists of a retrospective study with twenty-two individuals diagnosed with DRC: fourteen HD and eight CAPD, followed up in the dialysis center of Antonio Pedro University Hospital (HUAP) of Fluminense Federal Uni...It consists of a retrospective study with twenty-two individuals diagnosed with DRC: fourteen HD and eight CAPD, followed up in the dialysis center of Antonio Pedro University Hospital (HUAP) of Fluminense Federal University (UFF), between 2015 and 2017. Fifteen healthy control (HC) subjects were included, without diagnosed CKD. Patients with HIV positive, hepatitis A, B, and C, pregnant, cancer, smokers, alcoholics and those exposed to X-rays in the last 3 months, were excluded. Objectives: As oxidative stress and endothelial dysfunction may be linked to the higher prevalence of CVD in CKD patients, we measured the activities of the antioxidants enzymes: SOD and GPx and total NO levels in the plasma and serum of end-stage CKD patients undergoing dialysis therapy, comparing with the HC group. Methods: Quantification of NO levels was performed by fluorometric kit, while activities of SOD and GPx were determined using kinetic methods. Results: We found higher plasma SOD activity in HD (8.58 U/ml) and CAPD (10.14 U/ml), compared to C (3.73 U/ml) group, while GPx activity was decreased in HD (115.38 nmol/h/ml) and CAPD (122.76 nmol/h/ml) groups compared to HC group (275.83 nmol/h/ml). Total serum NO concentration was decreased in HD (14.09 pmol/μl) and CAPD (10.26 pmol/μl), compared to non-CKD patients (49.65 pmol/μl). Conclusion: Decreased total serum NO and GPx activities may lead to endothelial dysfunction and consequently a higher prevalence of CVD in CKD patients.展开更多
Within the CNS nuclear factor-kappa B(NF-κB) transcription factors are involved in a wide range of functions both in homeostasis and in pathology.Over the years,our and other groups produced a vast array of informa...Within the CNS nuclear factor-kappa B(NF-κB) transcription factors are involved in a wide range of functions both in homeostasis and in pathology.Over the years,our and other groups produced a vast array of information on the complex involvement of NF-κB proteins in different aspects of postnatal neurogenesis In particular,several extracellular signals and membrane receptors have been identified as being able to affect neural progenitor cells(NPC) and their progeny via NF-κB activation.A crucial role in the regulation of neuronal fate specification in adult hippocampal NPC is played by the NF-κB p50 subunit.NF-κB p50 KO mice display a remarkable reduction in adult hippocampal neurogenesis which correlates with a selective defect in hippocampal-dependent short-term memory.Moreover absence of NF-κB p50 can profoundly affect the in vitro proneurogenic response of adult hippocampal NPC(ahN PC) to several endogenous signals and drugs.Herein we briefly review the current knowledge on the pivotal role of NF-κB p50 in the regulation of adult hippocampal neurogenesis.In addition we discuss more recent data that further extend the relevance of NF-κB p50 to novel astroglia-derived signals which can influence neuronal specification of ahN PC and to astrocyte-NPC cross-talk.展开更多
The receptor for advanced glycation endproducts(RAGE)is a receptor of the immunoglobulin superfamily of cell surface molecules which plays important contributions under both physiological and pathological conditions...The receptor for advanced glycation endproducts(RAGE)is a receptor of the immunoglobulin superfamily of cell surface molecules which plays important contributions under both physiological and pathological conditions.Over the years extensive research work supported the detrimental role of RAGE in Alzheimer’s disease(AD)pathophysiology,ranging from its involvement in beta amyloid(Aβ)brain influx and clearance,展开更多
Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represent...Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.展开更多
The subgranular zone (SGZ) of the hippocampal dentate gyrus is one of the few central nervous system regions where generation of adult born neurons occurs physiologically.This process,referred to as adult hippocampal ...The subgranular zone (SGZ) of the hippocampal dentate gyrus is one of the few central nervous system regions where generation of adult born neurons occurs physiologically.This process,referred to as adult hippocampal neurogenesis (ahN),relies on the presence of neural progenitor cells (NPC) in the SGZ neurogenic niche.展开更多
文摘It consists of a retrospective study with twenty-two individuals diagnosed with DRC: fourteen HD and eight CAPD, followed up in the dialysis center of Antonio Pedro University Hospital (HUAP) of Fluminense Federal University (UFF), between 2015 and 2017. Fifteen healthy control (HC) subjects were included, without diagnosed CKD. Patients with HIV positive, hepatitis A, B, and C, pregnant, cancer, smokers, alcoholics and those exposed to X-rays in the last 3 months, were excluded. Objectives: As oxidative stress and endothelial dysfunction may be linked to the higher prevalence of CVD in CKD patients, we measured the activities of the antioxidants enzymes: SOD and GPx and total NO levels in the plasma and serum of end-stage CKD patients undergoing dialysis therapy, comparing with the HC group. Methods: Quantification of NO levels was performed by fluorometric kit, while activities of SOD and GPx were determined using kinetic methods. Results: We found higher plasma SOD activity in HD (8.58 U/ml) and CAPD (10.14 U/ml), compared to C (3.73 U/ml) group, while GPx activity was decreased in HD (115.38 nmol/h/ml) and CAPD (122.76 nmol/h/ml) groups compared to HC group (275.83 nmol/h/ml). Total serum NO concentration was decreased in HD (14.09 pmol/μl) and CAPD (10.26 pmol/μl), compared to non-CKD patients (49.65 pmol/μl). Conclusion: Decreased total serum NO and GPx activities may lead to endothelial dysfunction and consequently a higher prevalence of CVD in CKD patients.
基金supported by a grant from Fondazi one Cariplo to MG
文摘Within the CNS nuclear factor-kappa B(NF-κB) transcription factors are involved in a wide range of functions both in homeostasis and in pathology.Over the years,our and other groups produced a vast array of information on the complex involvement of NF-κB proteins in different aspects of postnatal neurogenesis In particular,several extracellular signals and membrane receptors have been identified as being able to affect neural progenitor cells(NPC) and their progeny via NF-κB activation.A crucial role in the regulation of neuronal fate specification in adult hippocampal NPC is played by the NF-κB p50 subunit.NF-κB p50 KO mice display a remarkable reduction in adult hippocampal neurogenesis which correlates with a selective defect in hippocampal-dependent short-term memory.Moreover absence of NF-κB p50 can profoundly affect the in vitro proneurogenic response of adult hippocampal NPC(ahN PC) to several endogenous signals and drugs.Herein we briefly review the current knowledge on the pivotal role of NF-κB p50 in the regulation of adult hippocampal neurogenesis.In addition we discuss more recent data that further extend the relevance of NF-κB p50 to novel astroglia-derived signals which can influence neuronal specification of ahN PC and to astrocyte-NPC cross-talk.
文摘The receptor for advanced glycation endproducts(RAGE)is a receptor of the immunoglobulin superfamily of cell surface molecules which plays important contributions under both physiological and pathological conditions.Over the years extensive research work supported the detrimental role of RAGE in Alzheimer’s disease(AD)pathophysiology,ranging from its involvement in beta amyloid(Aβ)brain influx and clearance,
基金This work was partially supported by the pharmaceutical company Astra Zeneca and by Fondazione Generali.
文摘Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.
基金supported by Progetti di Rilevante Interesse Nazionale(PRIN)2017。
文摘The subgranular zone (SGZ) of the hippocampal dentate gyrus is one of the few central nervous system regions where generation of adult born neurons occurs physiologically.This process,referred to as adult hippocampal neurogenesis (ahN),relies on the presence of neural progenitor cells (NPC) in the SGZ neurogenic niche.