scholarly journals The Long-Term Impact of Mild Traumatic Brain Injuries on Multiple Functional Outcomes and Epigenetics: A Pilot Study with College Students

Author(s):  
Hyunhwa Lee ◽  
Sungchul Lee ◽  
Ipuna Black ◽  
Laura Salado ◽  
Jonica Estrada ◽  
...  

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

2020 ◽  
Vol 10 (12) ◽  
pp. 4131 ◽  
Author(s):  
Hyunhwa Lee ◽  
Sungchul Lee ◽  
Ipuna Black ◽  
Laura Salado ◽  
Jonica Estrada ◽  
...  

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely assess long-term complications. This pilot study assessed and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated, including 14 healthy controls (64.3% females; mean age of 22.0) and 11 mTBI cases (27.3% females; mean age of 28.7 years) who self-reported mTBI history (63.6% multiple; 2.5 ± 1.29 injuries) with 7.1 years on average elapsed following the last injury. Every participant was assessed for cognitive (executive function, memory, and processing speed), psychological (depression, anxiety, and sleep disturbances), and visual function (by King–Devick and binocular accommodative tests); force-plate postural balance performance; and blood 5-mC% levels. Students with mTBI showed poorer episodic memory, severe anxiety, and higher blood 5-mC% ratio, compared to controls (all p’s < 0.05), which were still significant after adjusting for age. No differences were detected in sleep problems (after adjusting for age), visual function, and postural balance. These findings identified changes in multiple functions and peripheral epigenetics long after mTBI.


2020 ◽  
Vol 9 (6) ◽  
pp. 778-789
Author(s):  
Letícia Bernardini ◽  
Eduardo Barbosa ◽  
Mariele Feiffer Charão ◽  
Gabriela Goethel ◽  
Diana Muller ◽  
...  

Abstract Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.


Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 503-513 ◽  
Author(s):  
Benjamin B Parrott ◽  
John A Bowden ◽  
Satomi Kohno ◽  
Jessica A Cloy-McCoy ◽  
Matthew D Hale ◽  
...  

Epigenetic modifications are key mediators of the interactions between the environment and an organism's genome. DNA methylation represents the best-studied epigenetic modification to date and is known to play key roles in regulating transcriptional activity and promoting chromosome stability. Our laboratory has previously demonstrated the utility of the American alligator (Alligator mississippiensis) as a sentinel species to investigate the persistent effects of environmental contaminant exposure on reproductive health. Here, we incorporate a liquid chromatography–tandem mass spectrometry method to directly measure the total (global) proportion of 5-methyl-2′-deoxycytidine (5mdC) in ovarian and whole blood DNA from alligators. Global DNA methylation in ovaries was significantly elevated in comparison with that of whole blood. However, DNA methylation appeared similar in juvenile alligators reared under controlled laboratory conditions but originating from three sites with dissimilar environmental qualities, indicating an absence of detectable site-of-origin effects on persistent levels of global 5mdC content. Analyses of tissues across individuals revealed a surprising lack of correlation between global methylation levels in blood and ovary. In addition, global DNA methylation in blood samples from juvenile alligators was elevated compared with those from adults, suggesting that age, as observed in mammals, may negatively influence global DNA methylation levels in alligators. To our knowledge, this is the first study examining global levels of DNA methylation in the American alligator and provides a reference point for future studies examining the interplay of epigenetics and environmental factors in a long-lived sentinel species.


2014 ◽  
Vol 2014 (1) ◽  
pp. 2680 ◽  
Author(s):  
Gloria Chi* ◽  
Yongmei Liu ◽  
James MacDonald ◽  
R. Graham Barr ◽  
Kathleen Donohue ◽  
...  

2020 ◽  
Author(s):  
Remco Loos ◽  
Valeria Carola ◽  
Enrica Audero ◽  
Elena Brini ◽  
Luisa Lo Iacono ◽  
...  

AbstractVariation in DNA methylation between individuals has been shown to be influenced by both genetic and environmental factors. However, the relative impact of genetic and non-genetic factors on DNA methylation patterns across the mammalian genome has not been systematically studied. We performed whole-genome methylation analysis in two inbred mouse strains, revealing striking differences in the global distribution of DNA methylation. Although global methylation patterns were indistinguishable for most genomic features, a significant increase in the number of unmethylated CpG-island promoters and first exons was observed between strains. Experiments using F1 reciprocal hybrid strains demonstrated that the genotype of the mother dictated global DNA methylation patterns. Cross-fostering experiments ruled out a postnatal maternal effect on these differences and suggested that they were driven by a prenatal maternal effect, possibly via differential deposition of maternal gene products into the oocyte or uterine environment. These data demonstrate that maternal effects have a major impact on global DNA methylation patterns.


The Analyst ◽  
2017 ◽  
Vol 142 (11) ◽  
pp. 1900-1908 ◽  
Author(s):  
Md. Hakimul Haque ◽  
Ripon Bhattacharjee ◽  
Md. Nazmul Islam ◽  
Vinod Gopalan ◽  
Nam-Trung Nguyen ◽  
...  

We report a simple colorimetric (naked-eye) and electrochemical method for the rapid, sensitive and specific quantification of global methylation levels using only 25 ng of input DNA.


2016 ◽  
Vol 7 ◽  
Author(s):  
Raúl Alelú-Paz ◽  
Francisco J. Carmona ◽  
José V. Sanchez-Mut ◽  
Ariel Cariaga-Martínez ◽  
Ana González-Corpas ◽  
...  

PROTOPLASMA ◽  
2021 ◽  
Author(s):  
Sara Gomez-Cabellos ◽  
Peter E. Toorop ◽  
María Jesús Cañal ◽  
Pietro P. M. Iannetta ◽  
Eduardo Fernández-Pascual ◽  
...  

AbstractDespite the importance of dormancy and dormancy cycling for plants’ fitness and life cycle phenology, a comprehensive characterization of the global and cellular epigenetic patterns across space and time in different seed dormancy states is lacking. Using Capsella bursa-pastoris (L.) Medik. (shepherd’s purse) seeds with primary and secondary dormancy, we investigated the dynamics of global genomic DNA methylation and explored the spatio-temporal distribution of 5-methylcytosine (5-mC) and histone H4 acetylated (H4Ac) epigenetic marks. Seeds were imbibed at 30 °C in a light regime to maintain primary dormancy, or in darkness to induce secondary dormancy. An ELISA-based method was used to quantify DNA methylation, in relation to total genomic cytosines. Immunolocalization of 5-mC and H4Ac within whole seeds (i.e., including testa) was assessed with reference to embryo anatomy. Global DNA methylation levels were highest in prolonged (14 days) imbibed primary dormant seeds, with more 5-mC marked nuclei present only in specific parts of the seed (e.g., SAM and cotyledons). In secondary dormant seeds, global methylation levels and 5-mC signal where higher at 3 and 7 days than 1 or 14 days. With respect to acetylation, seeds had fewer H4Ac marked nuclei (e.g., SAM) in deeper dormant states, for both types of dormancy. However, the RAM still showed signal after 14 days of imbibition under dormancy-inducing conditions, suggesting a central role for the radicle/RAM in the response to perceived ambient changes and the adjustment of the seed dormancy state. Thus, we show that seed dormancy involves extensive cellular remodeling of DNA methylation and H4 acetylation.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 763-763
Author(s):  
Xinyin Jiang ◽  
Hunter Korsmo ◽  
Moshe Dembitzer ◽  
Sarah Khaldi ◽  
Shameera Sheeraz

Abstract Objectives Maternal obesity has long-term influence on metabolic health of offspring, partly through an epigenetic mechanism. Choline is a methyl donor which provides methyl groups for epigenetic modification such as DNA methylation. In this study, we examined the effect of maternal choline supplementation (MCS) on DNA methylation of offspring born to high-fat (HF) fed obese mouse dams. Methods C57BL/6J mice were fed either a 10% kcal normal fat (NF) or a 60% kcal HF diet with either 25 mM choline supplement or control drinking water from 4 weeks prior to mating until the end of gestation. The offspring were fed the HF diet for 6 weeks after weaning. We measured both global DNA methylation and site-specific methylation of several metabolic genes in the liver, visceral adipose tissue, and brain at both embryonic day E17.5 and after the post-weaning HF feeding. Results At E17.5, HF-MCS led to higher global DNA methylation in both fetal liver and brain. Methylation of one of the CpGs in the promoter region of Srebp1f (a gene that regulates lipogenesis) was also upregulated in the fetal liver by HF-MCS, accordingly there was lower expression of this gene (p &lt; 0.05). However, HF-MCS had opposite effects on global DNA methylation after 6 weeks of post weaning HF feeding than during the fetal period. At this time point, HF-MCS led to hypomethylation of liver and visceral adipose tissue (p &lt; 0.05). Global DNA methylation of the brain was decreased by post-weaning HF feeding but was not affected by maternal HF or MCS (p &lt; 0.01). Conclusions In conclusion, MCS during maternal obesity in the perinatal period influences offspring DNA methylation in a time-specific manner. The epigenetic programming effect of MCS needs to be evaluated in both short and long term in the offspring. Funding Sources NIGMS.


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