The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regenerati...The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Abstract The expression of early developmental markers such as doublecortin （DCX） and the polysialylated-neural cell adhesion molecule （PSA-NCAMIp has been used to identify immature neurons within canonical neuroge...Abstract The expression of early developmental markers such as doublecortin （DCX） and the polysialylated-neural cell adhesion molecule （PSA-NCAMIp has been used to identify immature neurons within canonical neurogenic niches. Additionally, DCX/PSA-NCAM ＋ immature neurons reside in cortical layer II of the paleocortex and in the paleo- and entorhinal cortex of mice and rats, respectively. These cells are also found in the neocortex of guinea pigs, rabbits, some afrotherian mammals, cats, dogs, non-human primates, and humans. The population of cortical DCX/PSA-NCAM ＋ immature neurons is generated prenatally as conclusively demonstrated in mice, rats, and guinea pigs. Thus, the majority of these cells do not appear to be the product of adult proliferative events. The immature neurons in cortical layer II are most abundant in the corlLices of young individuals, while very few DCX/PSA-NCAM ＋ cortical neurons can be detected in aged mammals. Maturation of DCX/PSA-NCAM ＋ cells into glutamatergic and GABAergic neurons has been proposed as an explanation for the age-dependent reduction in their population over time. In this review, we compile the recent information regarding the age-related decrease in the number of cortical DCX/PSA-NCAM ＋ neurons. We compare the distribution and fates of DCX/PSA-NCAM ＋ neurons among mammalian species and speculate their impact on cognitive function. To respond to the diversity of adult neurogenesis research produced over the last number of decades, we close this review by discussing the use and precision of the term ＂adult non-canonical neurogenesis.＂展开更多
基金supported by the FWF Special Research Program(SFB)F44(F4413-B23)"Cell Signaling in Chronic CNS Disorders",and through funding from the European Union’s Seventh Framework Program(FP7/2007-2013)under grant agreements n°HEALTH-F2-2011-278850(INMi ND),n°HEALTH-F2-2011-279288(IDEA),n°FP7-REGPOT-316120(Glow Brain)a startup grant from the Faculty Recharge Programme,University Grants Commission(UGC-FRP),New Delhi,India(to MK)+1 种基金a research grant from DST-SERB,New Delhi,India(EEQ/2016/000639)(to MK)an Early Career Research Award(ECR/2016/000741)(to MK)
文摘The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia.
基金part of the EU consortium DCogPlast‘Diet Cognition and Plasticity”funded by the Joint Programming Initiative“A Health Diet for a Healthy Life”(JPI-HDHL)via the BMWFW(BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)Further,LA was supported by the PMU-FFF ResearchFund(A-16/01/019-AIG)and BA by the PMU-Research and Innovation Fund(PMU-RIF)(project 2023-PRE-008-Altendorfer)+1 种基金PJL was supported by the Center for Urban Mental Health,and AK and PJL by Alzheimer Nederland and the ZonMW Program Mechanisms Of DEMentia(MODEM)and by the Gravitation program iCNS of the Dutch Research Council(NWO)CAL was supported by Grant PID2020-114921RB-C21,Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFES,CB16/10/00269,from the Instituto de Salud Carlos III all of them by“ERDF A way of making Europe”,the Generalitat de Catalunya’s Agency AGAUR of2021SGR00687 and ICREA Award.
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘Abstract The expression of early developmental markers such as doublecortin （DCX） and the polysialylated-neural cell adhesion molecule （PSA-NCAMIp has been used to identify immature neurons within canonical neurogenic niches. Additionally, DCX/PSA-NCAM ＋ immature neurons reside in cortical layer II of the paleocortex and in the paleo- and entorhinal cortex of mice and rats, respectively. These cells are also found in the neocortex of guinea pigs, rabbits, some afrotherian mammals, cats, dogs, non-human primates, and humans. The population of cortical DCX/PSA-NCAM ＋ immature neurons is generated prenatally as conclusively demonstrated in mice, rats, and guinea pigs. Thus, the majority of these cells do not appear to be the product of adult proliferative events. The immature neurons in cortical layer II are most abundant in the corlLices of young individuals, while very few DCX/PSA-NCAM ＋ cortical neurons can be detected in aged mammals. Maturation of DCX/PSA-NCAM ＋ cells into glutamatergic and GABAergic neurons has been proposed as an explanation for the age-dependent reduction in their population over time. In this review, we compile the recent information regarding the age-related decrease in the number of cortical DCX/PSA-NCAM ＋ neurons. We compare the distribution and fates of DCX/PSA-NCAM ＋ neurons among mammalian species and speculate their impact on cognitive function. To respond to the diversity of adult neurogenesis research produced over the last number of decades, we close this review by discussing the use and precision of the term ＂adult non-canonical neurogenesis.＂
