Redox potential defines functional states of adult hippocampal stem cells

Adusumilli, Vijay S.; Walker, Tara L.; Overall, Rupert W.; Klatt, Gesa M.; Zeidan, Salma Ahmed; Fischer, Tim J.; Zocher, Sara; Sykes, Alex M.; Reinhardt, Susanne; Dahl, Andreas; Kirova, Dilyana Georgieva; Mansfeld, Jörg; Rünker, Annette E.; Kempermann, Gerd

doi:10.1101/606186

Cited by 4 publications

(6 citation statements)

References 85 publications

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“…In general, quiescent NSCs are thought to have higher ROS levels, which gradually decrease during the progenitor stage, with low levels of ROS reported in mature neurons [128]. A recent study in mice suggested that NSCs require a spike in ROS levels before committing to proliferation and that this induction is prior to the redirection of cellular lipid metabolism to lipogenesis or induction of mitochondrial biogenesis [142]. Interestingly, the authors also suggested that NSCs can shift between different levels of proliferation induction, depending on ROS levels, without fully committing to enter neurogenesis [142].…”

Section: Redox State and Rosmentioning

confidence: 99%

“…A recent study in mice suggested that NSCs require a spike in ROS levels before committing to proliferation and that this induction is prior to the redirection of cellular lipid metabolism to lipogenesis or induction of mitochondrial biogenesis [142]. Interestingly, the authors also suggested that NSCs can shift between different levels of proliferation induction, depending on ROS levels, without fully committing to enter neurogenesis [142]. It is therefore likely that multiple signals have to come together to initiate neurogenesis.…”

Section: Redox State and Rosmentioning

confidence: 99%

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Metabolic regulation of neurodifferentiation in the adult brain

Maffezzini

Calvo‐Garrido

Wredenberg

et al. 2020

Cell. Mol. Life Sci.

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Understanding the mechanisms behind neurodifferentiation in adults will be an important milestone in our quest to identify treatment strategies for cognitive disorders observed during our natural ageing or disease. It is now clear that the maturation of neural stem cells to neurones, fully integrated into neuronal circuits requires a complete remodelling of cellular metabolism, including switching the cellular energy source. Mitochondria are central for this transition and are increasingly seen as the regulatory hub in defining neural stem cell fate and neurodevelopment. This review explores our current knowledge of metabolism during adult neurodifferentiation.

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Section: Redox State and Rosmentioning

confidence: 99%

Section: Redox State and Rosmentioning

confidence: 99%

Metabolic regulation of neurodifferentiation in the adult brain

Maffezzini

Calvo‐Garrido

Wredenberg

et al. 2020

Cell. Mol. Life Sci.

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“…Shifts to lower ROS content primed NPCs to a subsequent state transition, showing that lower ROS levels correlated with increased expression of proliferation and differentiation genes. In addition, NOX2 was not necessary for NPCs proliferation under physiological conditions, even if it has been reported that a transient NOX2-dependent ROS burst promotes exercise-induced recruitment of qNSCs to proliferation (Adusumilli et al, 2021). While this evidence seems to be in contrast with previous ones, they may not be mutually exclusive, because the transient nature of ROS and ROS signals likely triggers cell transitions without substantially altering ROS levels in the next cell type, especially if the ROS burst also activates antioxidative genes (Bueler, 2021).…”

Section: Ros Modulation Of Adult Neurogenesismentioning

confidence: 85%

Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming

Mormone

Iorio²,

Abate

et al. 2023

Front. Neurosci.

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Since the discovery of Neural Stem Cells (NSCs) there are still mechanism to be clarified, such as the role of mitochondrial metabolism in the regulation of endogenous adult neurogenesis and its implication in neurodegeneration. Although stem cells require glycolysis to maintain their stemness, they can perform oxidative phosphorylation and it is becoming more and more evident that mitochondria are central players, not only for ATP production but also for neuronal differentiation’s steps regulation, through their ability to handle cellular redox state, intracellular signaling, epigenetic state of the cell, as well as the gut microbiota-brain axis, upon dietary influences. In this scenario, the 8-oxoguanine DNA glycosylase (OGG1) repair system would link mitochondrial DNA integrity to the modulation of neural differentiation. On the other side, there is an increasing interest in NSCs generation, from induced pluripotent stem cells, as a clinical model for neurodegenerative diseases (NDs), although this methodology still presents several drawbacks, mainly related to the reprogramming process. Indeed, high levels of reactive oxygen species (ROS), associated with telomere shortening, genomic instability, and defective mitochondrial dynamics, lead to pluripotency limitation and reprogramming efficiency’s reduction. Moreover, while a physiological or moderate ROS increase serves as a signaling mechanism, to activate differentiation and suppress self-renewal, excessive oxidative stress is a common feature of NDs and aging. This ROS-dependent regulatory effect might be modulated by newly identified ROS suppressors, including the NAD+-dependent deacetylase enzymes family called Sirtuins (SIRTs). Recently, the importance of subcellular localization of NAD synthesis has been coupled to different roles for NAD in chromatin stability, DNA repair, circadian rhythms, and longevity. SIRTs have been described as involved in the control of both telomere’s chromatin state and expression of nuclear gene involved in the regulation of mitochondrial gene expression, as well as in several NDs and aging. SIRTs are ubiquitously expressed in the mammalian brain, where they play important roles. In this review we summarize the current knowledge on how SIRTs-dependent modulation of mitochondrial metabolism could impact on neurogenesis and neurodegeneration, focusing mainly on ROS function and their role in SIRTs-mediated cell reprogramming and telomere protection.

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“…However, given that the mechanisms underlying the high glucose-induced impairment of cell differentiation remain poorly understood, the application of PDLSCs to promote periodontal tissue regeneration in patients with diabetes is still in its infancy. Recently, increasing evidence has suggested that ROS play a vital role in the regulation of cell differentiation (17,18). Many studies also found that cells incubated under high glucose conditions showed dysregulation of intracellular ROS and NADPH, indicating that they might contribute to high glucoseinduced cellular osteogenic differentiation impairment (29, 36).…”

Section: Discussionmentioning

confidence: 99%

“…The exact mechanisms involved are still mysterious, but studies have revealed that the high glucose-caused cell dysfunction may be associated with inhibition of Glo1/AGE/RAGE axis (14), PI3K/Akt pathway (15), activation of MAPK pathway (13), excessive generation of reactive oxygen species (ROS) (16) and so on. Among the mechanisms studied, ROS, small molecules derived from oxygen and participate in regulating cell fate and cell proliferation and differentiation (17,18), has been recognized to be the most important contributor, and would be a potential target for periodontal treatment (19)(20)(21). Generally, increased ROS accumulation was found to be responsible for the reduced osteogenic differentiation potential of stem cells (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions

Zhang¹,

An²,

Sun³

et al. 2023

Front. Endocrinol.

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Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation. Although excessive accumulation of ROS has been found to be associated with high glucose-induced cell damage, the underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) is an important electron donor and functions as a critical ROS scavenger in antioxidant systems. It has been identified as a key mediator of various biological processes, including energy metabolism and cell differentiation. However, whether NADPH is involved in the dysregulation of ROS and further compromise of PDLSC osteogenic differentiation under high glucose conditions is still not known. In the present study, we found that PDLSCs incubated under high glucose conditions showed impaired osteogenic differentiation, excessive ROS accumulation and increased NADPH production. Furthermore, after inhibiting the synthesis of NADPH, the osteogenic differentiation of PDLSCs was significantly enhanced, accompanied by reduced cellular ROS accumulation. Our findings demonstrated the crucial role of NADPH in regulating cellular osteogenic differentiation under high glucose conditions and suggested a new target for rescuing high glucose-induced cell dysfunction and promoting tissue regeneration in the future.

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Redox potential defines functional states of adult hippocampal stem cells

Cited by 4 publications

References 85 publications

Metabolic regulation of neurodifferentiation in the adult brain

Metabolic regulation of neurodifferentiation in the adult brain

Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming

NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions

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