scholarly journals Mitochondrial DNA Toxicity in Forebrain Neurons Causes Apoptosis, Neurodegeneration, and Impaired Behavior

2010 ◽  
Vol 30 (6) ◽  
pp. 1357-1367 ◽  
Author(s):  
Knut H. Lauritzen ◽  
Olve Moldestad ◽  
Lars Eide ◽  
Harald Carlsen ◽  
Gaute Nesse ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Cognitive Abilities ◽  
Natural Aging ◽  
Base Substitution ◽  
Behavioral Alterations ◽  
Adult Mice ◽  
Progressive Loss ◽  
Forebrain Neurons ◽  
High Level

ABSTRACT Mitochondrial dysfunction underlying changes in neurodegenerative diseases is often associated with apoptosis and a progressive loss of neurons, and damage to the mitochondrial genome is proposed to be involved in such pathologies. In the present study we designed a mouse model that allows us to specifically induce mitochondrial DNA toxicity in the forebrain neurons of adult mice. This is achieved by CaMKIIα-regulated inducible expression of a mutated version of the mitochondrial UNG DNA repair enzyme (mutUNG1). This enzyme is capable of removing thymine from the mitochondrial genome. We demonstrate that a continual generation of apyrimidinic sites causes apoptosis and neuronal death. These defects are associated with behavioral alterations characterized by increased locomotor activity, impaired cognitive abilities, and lack of anxietylike responses. In summary, whereas mitochondrial base substitution and deletions previously have been shown to correlate with premature and natural aging, respectively, we show that a high level of apyrimidinic sites lead to mitochondrial DNA cytotoxicity, which causes apoptosis, followed by neurodegeneration.

MITOCHONDRIAL DNA POLYMORPHISM AND GYNODIOECY IN A NATURAL POPULATION OF ROSMARINUS OFFICINALIS L.

1999 ◽  
Vol 47 (2) ◽  
pp. 77-83 ◽  
Author(s):  
Pablo J. Hidalgo-Fernández ◽  
Rafael Pérez-Vicente ◽  
José Maldonado M. ◽  
José L. Ubera-Jiménez
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Rosmarinus Officinalis ◽  
Male Sterile ◽  
Standard Pattern ◽  
Mitochondrial Dna Polymorphism ◽  
Genome Variability ◽  
Dna Organization ◽  
Rosmarinus Officinalis L ◽  
High Level

Mitochondrial genome variability was studied in a gynodioecious population ofRosmarinus officinalisL. Analysis of mitochondrial DNA organization using Southern hybridization with probes for mitochondrial genescoxll, cob.andatp Arevealed a high level of mitochondrial polymorphism; 11 mitotypes were detected in a total of 27 individuals studied. One mitotype was particularly common among male fertile individuals. The remaining mitotypes were found in only one or two individuals, generally male sterile. Polymorphism was thus greater in male sterile than in male fertile individuals. The data presented here suggest that male sterility inRosmarinusis associated with the appearance of mitochondrial genome variants which differ from the standard pattern for male fertile plants.

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

scholarly journals Reduced Variation in Drosophila simulans Mitochondrial DNA

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1519-1528
Author(s):  
J William O Ballad ◽  
Joy Hatzidakis ◽  
Timothy L Karr ◽  
Martin Kreitman
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Evolutionary Dynamics ◽  
Selective Sweep ◽  
Mitochondrial Gene ◽  
Drosophila Simulans ◽  
Dramatic Reduction ◽  
Nucleotide Variability ◽  
Pooled Samples ◽  
Mitochondrial Gene Mutation

We investigated the evolutionary dynamics of infection of a Drosophila simulans population by a maternally inherited insect bacterial parasite, Wolbachia, by analyzing nucleotide variability in three regions of the mitochondrial genome in four infected and 35 uninfected lines. Mitochondrial variability is significantly reduced compared to a noncoding region of a nuclear-encoded gene in both uninfected and pooled samples of flies, indicating a sweep of genetic variation. The selective sweep of mitochondrial DNA may have been generated by the fixation of an advantageous mitochondrial gene mutation in the mitochondrial genome. Alternatively, the dramatic reduction in mitochondrial diversity may be related to Wolbachia.

Recent advances in animal model experimentation in autism research

2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Human Condition ◽  
Behavioral Alterations ◽  
Important Place ◽  
Adult Mice ◽  
Recent Advances ◽  
Model Study ◽  
Disease Biology ◽  
Animal Model Study

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

scholarly journals A GFP Reporter MR766-Based Flow Cytometry Neutralization Test for Rapid Detection of Zika Virus-Neutralizing Antibodies in Serum Specimens

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 66 ◽  
Author(s):  
Frumence ◽  
Viranaicken ◽  
Gadea ◽  
Desprès
Keyword(s):  
Flow Cytometry ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Health Concern ◽  
Structural Protein ◽  
Adult Mice ◽  
Gfp Reporter ◽  
Infected Cells ◽  
High Level

Zika virus (ZIKV) is an emerging arthropod-borne virus of major public health concern. ZIKV infection is responsible for congenital Zika disease and other neurological defects. Antibody-mediated virus neutralization is an essential component of protective antiviral immunity against ZIKV. In the present study, we assessed whether our GFP reporter ZIKV derived from African viral strain MR766 could be useful for the development of a flow cytometry neutralization test (FNT), as an alternative to the conventional plaque-reduction neutralization test (PRNT). To improve the efficacy of GFP-expressing MR766, we selected virus variant MR766GFP showing a high level of GFP signal in infected cells. A MR766GFP-based FNT was assayed with immune sera from adult mice that received ZIKBeHMR-2. The chimeric ZIKV clone ZIKBeHMR-2 comprises the structural protein region of epidemic strain BeH819015 into MR766 backbone. We reported that adult mice inoculated with ZIKBeHMR-2 developed high levels of neutralizing anti-ZIKV antibodies. Comparative analysis between MR766GFP-based FNT and conventional PRNT was performed using mouse anti-ZIKBeHMR-2 immune sera. Indistinguishable neutralization patterns were observed when compared with PRNT50 and FNT50. We consider that the newly developed MR766GFP-based FNT is a valid format for measuring ZIKV-neutralizing antibodies in serum specimens.

scholarly journals Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip

2007 ◽  
Vol 15 (11) ◽  
pp. 1145-1155 ◽  
Author(s):  
Marianne Lévêque ◽  
Sandrine Marlin ◽  
Laurence Jonard ◽  
Vincent Procaccio ◽  
Pascal Reynier ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Hearing Impairment ◽  
Dna Chip ◽  
Genome Screening ◽  
Syndromic Hearing Impairment
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