No game, more pain - Examining possible long term effects and underlying mechanisms of habitual violent video gaming on the acquired capability for suicide

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.

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Off to the right start: how pregnancy and early life can determine future animal health and production

Animal Production Science ◽

10.1071/an17014 ◽

2018 ◽

Vol 58 (3) ◽

pp. 459 ◽

Cited By ~ 1

Author(s):

K. L. Gatford ◽

C. T. Roberts ◽

K. L. Kind ◽

P. I. Hynd

Keyword(s):

Early Life ◽

Low Birthweight ◽

Animal Health ◽

Developmental Programming ◽

Developmental Trajectory ◽

Long Term Effects ◽

Prenatal Growth ◽

Underlying Mechanisms ◽

The Right

Animal producers are well aware that a low-birthweight animal is more likely to die in the first few days of life, and, if it survives, it is likely to perform poorly. We are now coming to appreciate that early life events can permanently change an animal’s developmental trajectory, also often referred to as developmental programming. This is an area of current interest in biomedicine, where the concept is known as the ‘developmental origins of health and disease’ (DOHaD). Current gaps in understanding include many of the underlying mechanisms, and whether and how we might intervene and restore the potential for healthy and productive development. This review introduces the biomedical perspective of developmental programming, reviews some of the evidence for long-term effects of early life exposures on welfare and productivity in animal production, with a focus on prenatal growth and maternal stress in pig production, and discusses options for intervening to improve long-term outcomes.

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Repetitive Mild Head Trauma Induces Activity-Mediated Lifelong Brain Deficits in a Novel Drosophila Model

10.1101/2021.02.09.430429 ◽

2021 ◽

Author(s):

Joseph A. Behnke ◽

Changtian Ye ◽

Aayush Setty ◽

Kenneth H. Moberg ◽

James Q. Zheng

Keyword(s):

Head Trauma ◽

Neuronal Excitability ◽

Brain Dysfunction ◽

Suitable Model ◽

Long Term Effects ◽

Head Impacts ◽

Brain Structure And Function ◽

Underlying Mechanisms ◽

And Function

AbstractMild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability in brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

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Acute Kahweol Treatment Attenuates Traumatic Brain Injury Neuroinflammation and Functional Deficits

Nutrients ◽

10.3390/nu11102301 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2301 ◽

Cited By ~ 3

Author(s):

Hung-Fu Lee ◽

Jhih Syuan Lin ◽

Che-Feng Chang

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Secondary Brain Injury ◽

Long Term Effects ◽

Short Term ◽

Functional Deficits ◽

Neurobehavioral Outcomes ◽

Underlying Mechanisms ◽

Neurobehavioral Deficits

Traumatic brain injury (TBI) affects millions worldwide with devastating long-term effects on health and cognition. Emerging data suggest that targeting the immune response may offer promising strategies to alleviate TBI outcomes; kahweol, an anti-inflammatory diterpene that remains in unfiltered coffee, has been shown to be beneficial in neuronal recovery. Here, we examined whether kahweol could alleviate brain trauma-induced injury in a mouse model of TBI and its underlying mechanisms. TBI was induced by controlled cortical impact (CCI) and various doses of kahweol were intraperitoneally administered following injury. Contusion volume, brain edema, neurobehavioral deficits, and protein expression and activity were evaluated in both short-term and long-term recovery. We found that kahweol treatments significantly reduced secondary brain injury and improved neurobehavioral outcomes in TBI mice. These changes were accompanied by the attenuation of proinflammatory cytokine secretion, decreased microglia/macrophage activation, and reduction of neutrophil and leukocyte infiltration. In addition, continuous kahweol treatment further improved short-term TBI outcomes compared to single-dosage. Collectively, our data showed that kahweol protects against TBI by reducing immune responses and may serve as a potential therapeutic intervention for TBI patients.

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Physiology in Medicine: update on lifestyle determinants of postprandial triacylglycerolemia with emphasis on the Mediterranean lifestyle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00245.2015 ◽

2015 ◽

Vol 309 (5) ◽

pp. E440-E449 ◽

Cited By ~ 3

Author(s):

Maria I. Maraki ◽

Labros S. Sidossis

Keyword(s):

Independent Risk Factor ◽

Postprandial Lipemia ◽

Protective Role ◽

Long Term Effects ◽

Monounsaturated Fat ◽

Short Term ◽

Postprandial State ◽

The Mediterranean ◽

Underlying Mechanisms

This review updates the effect of lifestyle on plasma triacylglycerols (TAG) in the postprandial state, commonly reported as postprandial lipemia (PPL), an independent risk factor for cardiovascular diseases (CVD). Numerous studies have shown that Mediterranean diet may reduce PPL. However, most of these studies were focused on the type of fat (i.e., monounsaturated fat from olive oil), and the other components of the Mediterranean lifestyle were neglected. Physical activity, an integral part of this lifestyle, is widely investigated on its own and shown to reduce PPL. In addition, preliminary results of studies examining other Mediterranean “ingredients”, such as legumes, fish, and herbs, showed additional benefits; however, data on the long-term effects are limited. More studies are needed to confirm short-term results and investigate the effects of the whole Mediterranean lifestyle on PPL and whether these effects mediate its protective role on CVD. Moreover, investigation of the effects in nonhealthy populations and the underlying mechanisms would be clinically helpful in individualizing the appropriate intervention.

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Ultraviolet radiation modulates DNA methylation in melanocytes

10.1101/2021.10.14.464470 ◽

2021 ◽

Author(s):

Sarah Preston-Alp ◽

Jaroslav Jelinek ◽

Jean-Pierre Issa ◽

M. Raza Zaidi

Keyword(s):

Dna Methylation ◽

Ultraviolet Radiation ◽

Molecular Mechanisms ◽

Long Term Effects ◽

Induced Mutations ◽

Cpg Sites ◽

Intergenic Regions ◽

Underlying Mechanisms

Ultraviolet radiation (UVR) is the principal causal factor for melanoma; albeit the underlying mechanisms remain unclear. While the mutagenic properties of UVR are irrefutable, the role of UVR-induced mutations in the initiation of melanoma is controversial which highlights the gap in our knowledge of the initial critical molecular mechanisms of UVR-induced melanomagenesis. To investigate the potential non-mutational mechanisms of UVR-induced melanomagenesis, we studied the role of UVR in modulating DNA methylation changes in melanocytes via next-generation sequencing-based methodologies. Here we show that UVR directly causes stable changes in the DNA methylome and transcriptome, one month after exposure. Genomic features associated with transcription were protected from 5mC alterations whereas CpG sites found in intergenic regions were more likely to be affected. Additionally, the long-term effects of UVR seem to perturb signaling pathways important for melanocyte biology. Interestingly, UVR-sensitive CpG sites were found to be prognostic of overall patient survival and highlighted a subset of CpG sites that may be relevant in melanomagenesis.

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Maternal mood in pregnancy: fetal origins of child neurodevelopment

10.1093/med/9780198749547.003.0003 ◽

2017 ◽

Author(s):

Vivette Glover ◽

Thomas G. O’Connor ◽

Kieran O’Donnell

Keyword(s):

Postnatal Period ◽

Long Term Effects ◽

Fetal Origins ◽

Infant Outcomes ◽

Maternal Mood ◽

Child Neurodevelopment ◽

Underlying Mechanisms ◽

Anxiety Depression ◽

In Pregnancy

Women experience as many symptoms of anxiety, depression, and stress during pregnancy as in the postnatal period. This can affect not only the woman herself but also the development of her fetus, and have long-term effects on several different outcomes including the cognitive ability and behaviour of her child, although most children are not affected. The particular outcomes affected may depend on the timing of the exposure, specific genetic vulnerabilities, and the quality of postnatal care provided. Recent research has shown that increased maternal anxiety is associated with altered placental function, and a greater association between maternal and fetal cortisol. This interrelationship of hormonal associations during the fetal stage could potentially impact on fetal/infant outcomes, and supports the need for continuing research in the field. Chapter 3 covers studies on maternal mood in pregnancy and explores the underlying mechanisms and types of stress.

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Exposure-Based Treatment for Obsessive Compulsive Disorder

10.1093/oxfordhb/9780195376210.013.0071 ◽

2012 ◽

Cited By ~ 1

Author(s):

Jonathan S. Abramowitz ◽

Steven Taylor ◽

Dean McKay

Keyword(s):

Obsessive Compulsive Disorder ◽

Psychosocial Interventions ◽

Future Research ◽

Long Term Effects ◽

Obsessive Compulsive ◽

Research Directions ◽

Compulsive Disorder ◽

Future Research Directions ◽

Underlying Mechanisms

Exposure and response prevention (ERP) is one of the oldest and most effective treatments for obsessive compulsive disorder. The present chapter describes the empirical foundations, development, delivery, and latest research on ERP. Commonly used methods and procedural variants of ERP are described, along with findings concerning the underlying mechanisms of action. The efficacy of ERP in relation to other treatments is discussed, in addition to research on the long-term effects of ERP and its effects in non-research settings. Pretreatment predictors of the outcome of treatments using ERP are also considered. Efforts to improve treatment outcome are discussed, including research into the benefits of combining ERP with other psychosocial interventions such as cognitive therapy, or with particular medications. The chapter concludes by considering important future research directions for improving the outcome of treatment packages that include ERP.

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Exercise during pregnancy and its impact on mothers and offspring in humans and mice

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000617 ◽

2017 ◽

Vol 9 (1) ◽

pp. 63-76 ◽

Cited By ~ 10

Author(s):

N. Ferrari ◽

I. Bae-Gartz ◽

C. Bauer ◽

R. Janoschek ◽

I. Koxholt ◽

...

Keyword(s):

Weight Gain ◽

High Fat Diet ◽

Exercise Program ◽

Protective Effects ◽

Long Term Effects ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Exercise During Pregnancy

Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring’s weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.

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Ovarian Dysfunction in Fetally Irradiated Beagles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080717 ◽

1977 ◽

Vol 35 ◽

pp. 658-659

Author(s):

T. M. Seed ◽

M. H. Sanderson ◽

D. L. Gutzeit ◽

T. E. Fritz ◽

D. V. Tolle ◽

...

Keyword(s):

Gamma Rays ◽

Low Dose ◽

Long Term Effects ◽

Ovarian Dysfunction ◽

Dose Rates ◽

Highly Sensitive ◽

Microscopic Evaluation ◽

Ovarian Pathology ◽

Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

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