DNA repair in neurons: So if they don’t divide what's to repair?

Fishel, Melissa L.; Vasko, Michael R.; Kelley, Mark R.

doi:10.1016/j.mrfmmm.2006.06.007

Cited by 228 publications

(165 citation statements)

References 115 publications

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“…Cell cycledependent effects in immortalized neuronal cell models may significantly alter the toxic response compared to post-mitotic neuronal cells in culture [75,76]. While NGF-differentiated neuronal cultures may imperfectly model the complexity of NO-mediated events in vivo, they point to the importance of using post-mitotic cells for study of neuronal cell death and neurodegeneration in vitro.…”

Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor Potentiates p53 DNA Binding but Inhibits Nitric Oxide-Induced Apoptosis in Neuronal PC12 Cells

Brynczka

Merrick

2007

Neurochem Res

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NGF is recognized for its role in neuronal differentiation and maintenance. Differentiation of PC12 cells by NGF involves p53, a transcription factor that controls growth arrest and apoptosis. We investigated NGF influence over p53 activity during NO-induced apoptosis by sodium nitroprusside in differentiated and mitotic PC12 cells. NGF-differentiation produced increased p53 levels, nuclear localization and sequence-specific DNA binding. Apoptosis in mitotic cells also produced these events but the accompanying activation of caspases 1-10 and mitochondrial depolarization were inhibited during NGF differentiation and could be reversed in p53-silenced cells. Transcriptional regulation of PUMA and survivin expression were not inhibited by NGF, although NO-induced mitochondrial depolarization was dependent upon de novo gene transcription and only occurred in mitotic cells. We conclude that NGF mediates prosurvival signaling by increasing factors such as Bcl-2 and p21 Waf1/Cip1 without altering p53 transcriptional activity and prevents mitochondrial depolarization and caspase activation to inhibit apoptosis.

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Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor Potentiates p53 DNA Binding but Inhibits Nitric Oxide-Induced Apoptosis in Neuronal PC12 Cells

Brynczka

Merrick

2007

Neurochem Res

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“…Base excision repair is the primary repair mechanism in the brain that removes lesions from DNA. Several enzymes are required to convert the damaged DNA [30]. One enzyme that plays a crucial role in this process is uracil-DNA glycosylase (UNG); it removes mismatched uracil from single and double stranded DNA [31].…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji

Farr

Lips

et al. 2015

Behavioural Brain Research

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(2015) Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 283 . pp. 215-226. ISSN 1872-7549 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32983/9/UNG_FADD_20140826_manuscript_final.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. ABSTRACTDietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders.Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfusion in an animal model. Ung+/+ and Ung−/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung−/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung+/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung−/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion o...

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“…Base excision repair (BER), the main repair pathway for the removal of oxidative base modifications from DNA, plays a vital role in the development and maintenance of the central nervous system (Fishel et al, 2006). The first step in BER is the removal of the damaged base by substrate-specific DNA glycosylases to generate an abasic site which is then cleaved by an AP lyase or AP endonuclease (APE).…”

Section: Introductionmentioning

confidence: 99%

DNA base excision repair activities in mouse models of Alzheimer's disease

Weissman

Souza-Pinto

Mattson

et al. 2009

Neurobiology of Aging

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Alzheimer's disease (AD) has been correlated with elevated levels of oxidative DNA damage. Base excision repair (BER) is the main repair pathway for the removal of oxidative DNA base modifications. We have recently found significant functional deficiencies in BER in brains of sporadic AD and amnestic mild cognitive impairment patients. In this study we tested whether altered BER activities are associated with appearance of symptoms in different brain regions of presymptomatic and symptomatic mice harboring mutant APP alone or in combination with Tau and PS1. Our results suggest that unlike in humans, the development of AD-like pathology in the studied mouse models is not associated with deficiencies in BER. KeywordsAlzheimers disease; DNA repair; oxidative stress; oxidative DNA damage Alzheimer's disease (AD) has been associated with elevated oxidative DNA damage in the human brain (Gabbita et al., 1998). Base excision repair (BER), the main repair pathway for the removal of oxidative base modifications from DNA, plays a vital role in the development and maintenance of the central nervous system (Fishel et al., 2006). The first step in BER is the removal of the damaged base by substrate-specific DNA glycosylases to generate an abasic site which is then cleaved by an AP lyase or AP endonuclease (APE). This is followed by incorporation of one or several nucleotides into the gap by DNA polymerase and strand ligation by a DNA ligase. We have recently found significant functional deficiencies in BER in brains of sporadic AD and amnestic mild cognitive impairment (MCI) patients due to limited DNA base damage processing by DNA glycosylases and reduced DNA synthesis capacity by polymerase β (polβ) (Weissman et al., 2007). However, the question of how BER deficiency is involved in the progression of AD has yet to be answered.

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DNA repair in neurons: So if they don’t divide what's to repair?

Cited by 228 publications

References 115 publications

Nerve Growth Factor Potentiates p53 DNA Binding but Inhibits Nitric Oxide-Induced Apoptosis in Neuronal PC12 Cells

Nerve Growth Factor Potentiates p53 DNA Binding but Inhibits Nitric Oxide-Induced Apoptosis in Neuronal PC12 Cells

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

DNA base excision repair activities in mouse models of Alzheimer's disease

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