Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors

Tsatmali, Marina; Walcott, Elisabeth C.; Crossin, Kathryn L.

doi:10.1016/j.brainres.2005.01.087

Cited by 126 publications

(94 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present results suggest that Apocynin and 5-HD act by stimulating differentiation of mesencephalic precursors toward the DA phenotype. The results are consistent with those of previous studies, which have suggested that the redox state modulates differentiation of mesencephalic precursors (Studer et al, 2000;Rodriguez-Pallares et al, 2001Tsatmali et al, 2005), and with those of studies that have suggested that ROS levels affect the phenotype of cells in culture (Li et al, 2006;Xiao et al, 2009), including neurons (Tsatmali et al, 2006).…”

Section: Discussionsupporting

confidence: 92%

“…The number of proliferating cells further decreases after induction of the differentiation, as expected after withdrawal of the mitogens from the cell culture (Studer et al, 2000;Ebert et al, 2008). Several previous studies have suggested that intracellular levels of ROS modulate neuronal differentiation, and it has been observed that cell fractions exhibiting low levels of ROS contain proliferative progenitor cells, while newly generated neurons express high levels of ROS (Katoh et al, 1997;Goldsmit et al, 2001;Wang et al, 2007;Tsatmali et al, 2005); this was also confirmed in the present study by DHE labeling. Because undifferentiated neural stem cells contain very low levels of ROS, it is reasonable to believe that further ROS inhibition has no significant effects.…”

Section: Discussionsupporting

confidence: 87%

“…In previous studies with antioxidants (Rodriguez-Pallares et al, 2001 and preliminary experiments with Apo or 5-HD, we did not observe effects on DA cell generation when treatments were administered during the first week of proliferation (i.e., 1 to 7 DIV). This is in accordance with previous studies that observed that proliferative progenitor cell exhibited very low levels of ROS, while ROS increased to high levels in newly generated neurons (Katoh et al, 1997;Goldsmit et al, 2001;Tsatmali et al, 2005;Wang et al, 2007). Therefore, treatments were added to the medium during the late proliferation period (i.e., 7 to 14 DIV) or the differentiation period (i.e., 14 to 21DIV), for an incubation period of 7 days (i.e., 7 days of treatment), except when otherwise stated.…”

Section: Experimental Procedures Isolation and Culture Of Mesencephalsupporting

confidence: 93%

“…In addition, several previous studies have demonstrated that cell death of neural precursors within proliferating clusters is relatively rare compared with that of dissociated cells (Studer et al, 1998). The percentage of TUNEL-positive cells in clusters reported by previous studies was around 2-5% (Studer et al, 1998;Lee et al, 2003;Tsatmali et al, 2005), and it has been suggested that cell-cell contact may provide sufficient survival signals on the clustered precursors so that treatments no longer have any antiapoptotic or proapoptotic effect on the clustered cells (Peluso, 2000;Pilling et al, 2000;Lee et al, 2003). The results of the present study on apoptotic cell death confirm the low rate of apoptosis under the present experimental conditions and that Apo and 5-HD do not affect survival of DAergic precursors in the cultures.…”

Section: Discussionmentioning

confidence: 91%

See 3 more Smart Citations

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Rodríguez‐Pallares

Joglar

Díaz-Ruiz

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

Reactive oxygen species signaling has been suggested to regulate stem cell development. In the present study, we treated neurospheres of rat mesencephalic precursors with inhibitors of the NADPH oxidase complex and mitochondrial ATP-sensitive potassium (mitoKATP) channel blockers during the proliferation and/or the differentiation periods to study the effects on generation of dopaminergic neurons. Treatment with low doses (100 or 250 mM) of the NADPH inhibitor apocynin during the proliferation period increased the generation of dopaminergic neurons. However, higher doses (1 mM) were necessary during the differentiation period to induce the same effect. Treatment with general (glibenclamide) or mitochondrial (5-hydroxydecanoate) KATP channel blockers during the proliferation and differentiation periods increased the number of dopaminergic neurons. Furthermore, neither increased proliferation rate nor apoptosis had a major role in the observed increase in generation of dopaminergic neurons, which suggests that the redox state is able to regulate differentiation of precursors into dopaminergic neurons. Developmental Dynamics 239:3247-3259,

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 87%

Section: Experimental Procedures Isolation and Culture Of Mesencephalsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

See 2 more Smart Citations

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Rodríguez‐Pallares

Joglar

Díaz-Ruiz

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that differentiation of neurons is associated with up-regulation of ROS and down-regulation of antioxidants (Tsatmali et al, 2005). This would put a heavier demand on cells' capacity to repair ROS damage during differentiation, just when a reduction of overall NER appears also to occur (Nouspikel and Hanawalt, 2000).…”

Section: Dna Damage and Repair In Neurodegenerationmentioning

confidence: 99%

Clinical implications of the basic defects in Cockayne syndrome and xeroderma pigmentosum and the DNA lesions responsible for cancer, neurodegeneration and aging

Cleaver

Revet

2008

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

Cancer, aging, and neurodegeneration are all associated with DNA damage and repair in complex fashions. Aging appears to be a cell and tissue-wide process linked to the insulin-dependent pathway in several DNA repair deficient disorders, especially in mice. Cancer and neurodegeneration appear to have complementary relationships to DNA damage and repair. Cancer arises from surviving cells, or even stem cells, that have down-regulated many pathways, including apoptosis, that regulate genomic stability in a multi-step process. Neurodegeneration however occurs in nondividing neurones in which the persistence of apoptosis in response to reactive oxygen species is, itself, pathological. Questions that remain open concern: sources and chemical nature of naturally occurring DNA damaging agents, especially whether mitochondria are the true source; the target tissues for DNA damage and repair; do the human DNA repair deficient diseases delineate specific pathways of DNA damage relevant to clinical outcomes; if naturally occurring reactive oxygen species are pathological in human repair deficient disease, would anti-oxidants or anti-apoptotic agents be feasible therapeutic agent?

show abstract

Impact of lactic acid on cell proliferation and free radical‐induced cell death in monolayer cultures of neural precursor cells

Lampe

Namba

Silverman

et al. 2009

Biotech & Bioengineering

View full text Add to dashboard Cite

Biomaterials prepared from polyesters of lactic acid and glycolic acid, or a mixture of the two, degrade in the presence of water into the naturally occurring metabolites, lactic acid and glycolic acid. While the lactic acid degradation product that is released from biomaterials is well-tolerated by the body, lactic acid can influence the metabolic function of cells; it can serve as an energy substrate for cells, and has been shown to have antioxidant properties. Neural precursor cells, a cell population of considerable interest as a source of cells for neural tissue regeneration strategies, generate a high amount of reactive oxygen species, and when associated with a degradable biomaterial, may be impacted by released lactic acid. In this work, the effect of lactic acid on a neural cell population containing proliferative neural precursor cells was examined in monolayer culture. Lactic acid was found to scavenge exogenously added free radicals produced in the presence of either hydrogen peroxide or a photoinitiator (I2959) commonly utilized in the preparation of photopolymerizable biomaterials. In addition to its effect on exogenously added free radicals, lactic acid reduced intracellular redox state, increased the proliferation of the cell population, and modified the cell composition. The findings of this study provide insight into the role that lactic acid plays naturally on developing neural cells and are also of interest to biomaterials scientists that are focused on the development of degradable lactic-acid based polymers for cell culture devices. The effect of lactic acid on other cell populations may differ and should be characterized to best understand how cells function in degradable cell culture devices.

show abstract

Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors

Cited by 126 publications

References 89 publications

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Clinical implications of the basic defects in Cockayne syndrome and xeroderma pigmentosum and the DNA lesions responsible for cancer, neurodegeneration and aging

Impact of lactic acid on cell proliferation and free radical‐induced cell death in monolayer cultures of neural precursor cells

Contact Info

Product

Resources

About