The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The "spectrum" of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments which can have profound and lasting effects on individuals throughout their lives, impacting their health, social interactions, psychological well-being, and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress in epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

Quadrato Motor Training (QMT) is associated with DNA methylation changes at DNA repeats: A pilot study.

The control of non-coding repeated DNA by DNA methylation plays an important role in genomic stability, contributing to health and healthy aging. Mind-body practices can elicit psychophysical wellbeing via epigenetic mechanisms, including DNA methylation. However, in this context the effects of movement meditations have rarely been examined. Consequently, the current study investigates the effects of a specifically structured movement meditation, called the Quadrato Motor Training (QMT) on psychophysical wellbeing and on the methylation level of repeated sequences. An 8-week daily QMT program was administered to healthy women aged 40-60 years and compared with a passive control group matched for gender and age. Psychological well-being was assessed within both groups by using self-reporting scales, including the Meaning in Life Questionnaire [MLQ] and Psychological Wellbeing Scale [PWB]). DNA methylation profiles of repeated sequences (ribosomal DNA, LINE-1 and Alu) were determined in saliva samples by deep-sequencing. In contrast to controls, the QMT group exhibited increased Search for Meaning, decreased Presence of Meaning and increased Positive Relations, suggesting that QMT may lessen the automatic patterns of thinking. In the QMT group, we also found site-specific significant methylation variations in ribosomal DNA and LINE-1 repeats, consistent with increased genome stability. Finally, the correlations found between changes in methylation and psychometric indices (MLQ and PWB) suggest that the observed epigenetic and psychological changes are interrelated. Collectively, the current results indicate that QMT may improve psychophysical health trajectories by influencing the DNA methylation of specific repetitive sequences.

Quadrato motor training (QMT) influences IL-1ß expression and creativity: Implications for inflammatory state reduction and cognitive enhancement.

Mind-body practices and meditation have been increasingly studied in recent years due to their beneficial effects on cognition, and physical and psychological health. Growing evidence suggests that these practices could be utilized as interventions to impact age-related biological processes, such as cognitive decline, inflammation, and homeostatic dysregulation. Indeed, it has been reported that mindful meditation may induce neuroplasticity in brain regions involved in control of attention, emotional regulation, and self-awareness. In the current research we studied the effects of a recently developed movement meditation, named the Quadrato Motor Training (QMT), on the proinflammatory cytokine Interleukin-1beta (IL-1ß), utilizing a pre-post design. In addition to its role in the immune system, IL-1ß is also an important mediator of neuroimmune responses related to sickness behavior, and plays a role in complex cognitive processes, such as synaptic plasticity, neurogenesis, and neuromodulation. Thirty healthy participants were divided in two groups, one performing QMT for 2 months, and one passive control group. Salivary IL-1ß expression was examined by ELISA to measure protein levels and by qRT-PCR to quantify mRNA. In addition, the methylation profile of the IL-1ß promoter was examined. All participants further conducted the Alternate Uses Task (AUT) and Hidden Figure Test (HFT), to measure their creativity and spatial cognition. The results showed that, following QMT practice, IL-1ß protein level decreased and creativity increased, compared to the control group. These data demonstrate that QMT may help reduce inflammatory states and promote cognitive improvement, highlighting the importance of non-pharmacological approaches to health and well-being.

On the road to resilience: Epigenetic effects of meditation.

Many environmental and lifestyle related factors may influence the physiology of the brain and body by acting on fundamental molecular pathways, such as the hypothalamus-pituitary-adrenal axis (HPA) and the immune system. For example, stressful conditions created by adverse early-life events, unhealthy habits and low socio-economic status may favor the onset of diseases linked to neuroendocrine dysregulation, inflammation and neuroinflammation. Beside pharmacological treatments used in clinical settings, much attention has been given to complementary treatments such as mind-body techniques involving meditation that rely on the activation of inner resources to regain health. At the molecular level, the effects of both stress and meditation are elicited epigenetically through a set of mechanisms that regulate gene expression as well as the circulating neuroendocrine and immune effectors. Epigenetic mechanisms constantly reshape genome activities in response to external stimuli, representing a molecular interface between organism and environment. In the present work, we aimed to review the current knowledge on the correlation between epigenetics, gene expression, stress and its possible antidote, meditation. After introducing the relationship between brain, physiology, and epigenetics, we will proceed to describe three basic epigenetic mechanisms: chromatin covalent modifications, DNA methylation and non-coding RNAs. Subsequently, we will give an overview of the physiological and molecular aspects related to stress. Finally, we will address the epigenetic effects of meditation on gene expression. The results of the studies reported in this review demonstrate that mindful practices modulate the epigenetic landscape, leading to increased resilience. Therefore, these practices can be considered valuable tools that complement pharmacological treatments when coping with pathologies related to stress.

Arabidopsis thaliana sirtuins control proliferation and glutamate dehydrogenase activity.

Sirtuins are part of a gene family of NAD-dependent deacylases that act on histone and non-histone proteins and control a variety of activities in all living organisms. Their roles are mainly related to energy metabolism and include lifetime regulation, DNA repair, stress resistance, and proliferation. A large amount of knowledge concerning animal sirtuins is available, but data about their plant counterparts are scarce. Plants possess few sirtuins that have, like in animals, a recognized role in stress defense and metabolism regulation. However, engagement in proliferation control, which has been demonstrated for mammalian sirtuins, has not been reported for plant sirtuins so far. In this work, srt1 and srt2 Arabidopsis mutant seedlings have been used to evaluate in vivo the role of sirtuins in cell proliferation and regulation of glutamate dehydrogenase, an enzyme demonstrated to be involved in the control of cell cycle in SIRT4-defective human cells. Moreover, bioinformatic analyses have been performed to elucidate sequence, structure, and function relationships between Arabidopsis sirtuins and between each of them and the closest mammalian homolog. We found that cell proliferation and GDH activity are higher in mutant seedlings, suggesting that both sirtuins exert a physiological inhibitory role in these processes. In addition, mutant seedlings show plant growth and root system improvement, in line with metabolic data. Our data also indicate that utilization of an easy to manipulate organism, such as Arabidopsis plant, can help to shed light on the molecular mechanisms underlying the function of genes present in interkingdom species.

Molecules of Silence: Effects of Meditation on Gene Expression and Epigenetics.

Many studies have consistently demonstrated an epigenetic link between environmental stimuli and physiological as well as cognitive responses. Epigenetic mechanisms represent a way to regulate gene activity in real time without modifying the DNA sequence, thus allowing the genome to adapt its functions to changing environmental contexts. Factors such as lifestyle, behavior, and the practice of sitting and moving mindful activities have been shown to be important means of environmental enrichment. Such practices, which include mindfulness meditation, Vipassana, Yoga, Tai Chi, and Quadrato Motor Training, have been reported to positively impact well-being. In fact, they can be considered emotional and attentional regulatory activities, which, by inducing a state of greater inner silence, allow the development of increased self-awareness. Inner silence can therefore be considered a powerful tool to counteract the negative effects of overabundant environmental noise, thanks to its power to relieve stress-related symptoms. Since all these positive outcomes rely on physiological and biochemical activities, the molecular and epigenetic mechanisms influenced by different mindful practices have recently started to be investigated. Here, we review some of the findings that could allow us to uncover the mechanisms by which specific practices influence well-being.

Influence of Quadrato Motor Training on Salivary proNGF and proBDNF.

Previous studies demonstrated exercise-induced modulation of neurotrophins, such as Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Yet, no study that we are aware of has examined their change as a function of different training paradigms. In addition, the understanding of the possible training-induced relationship between NGF and BDNF change is still lacking. Consequently, in the current study we examined the effect of a Walking Training (WT) and of Quadrato Motor Training (QMT) on NGF and BDNF precursors (proNGF and proBDNF). QMT is a specifically structured sensorimotor training that involves sequences of movements based on verbal commands, that was previously reported to improve spatial cognition, reflectivity, creativity as well as emotion regulation and general self-efficacy. In addition, QMT was reported to induce electrophysiological and morphological changes, suggesting stimulation of neuroplasticity processes. In two previous independent studies we reported QMT-induced changes in the salivary proNGF and proBDNF levels. Our present results demonstrate that following 12 weeks of daily QMT practice, proNGF level increases while proBDNF showed no significant change. More importantly, while no correlation between the two neurotrophins prior to training was detectable, there was a significant correlation between change in proNGF and proBDNF levels. Taken together the current results suggest that the two neurotrophins undergo a complex modulation, likely related to the different pathways by which they are produced and regulated. Since variations of these neurotrophins have been previously linked to depression, stress and anxiety, the current study may have practical implications and aid in understanding the possible physiological mechanisms that mediate improved well-being, and the dynamic change of neurotrophins as a result of training.

Creating Well-Being: Increased Creativity and proNGF Decrease following Quadrato Motor Training.

Mind-body practices (MBP) are known to induce electrophysiological and morphological changes, whereas reports related to changes of neurotrophins are surprisingly scarce. Consequently, in the current paper, we focused on the Quadrato motor training (QMT), a newly developed whole-body movement-based MBP, which has been reported to enhance creativity. Here we report the effects of 4 weeks of daily QMT on creativity and proNGF level in two interrelated studies. In Study A, we examined the effects of QMT compared with a walking training (WT) in healthy adults, utilizing the alternate uses task. In contrast with the WT, QMT resulted in increased creativity. In addition, the change in creativity negatively correlated with the change in proNGF levels. In Study B, we examined QMT effects on creativity and additional metacognitive functions in children, using a nonintervention group as control. Similar to Study A, following QMT, we found a negative correlation of proNGF with creativity, as well as working memory updating and planning ability. Together, the current results point to the relationship between increased creativity and decreased proNGF following MBP. Thus, the current research emphasizes the importance of widening the scope of examination of "MBP in motion" in relation to metacognition and well-being.

Sir2 is involved in the transcriptional modulation of NHP6A in Saccharomyces cerevisiae.

The Sir proteins, namely Sir2, 3 and 4, have roles related to heterochromatin, but genome-wide studies have revealed their presence at many euchromatic loci, although the functional meaning of this is still not clear. Nhp6a is an abundant HMG-like protein in yeast, which has a role in transcription by modulating chromatin structure and nucleosome number. Although much is known about its structure and function, information regarding its regulation is scarce. NHP6A, among other genes, emerges in ChIP-on chip studies of global Sir proteins binding, suggesting it could be regulated by SIR. We have investigated NHP6A expression in sir deletion mutants as well as in SIR2 overexpressing conditions. In addition, we have asked if the Sir2 deacetylation activity is involved by using conditions that either inhibit (treatment with nicotinamide) or enhance (calorie restriction conditions) Sir2 activity. We have found that, consistent with previous microarray studies, NHP6A expression undergoes a slight increase in sir mutant strains, but is strongly repressed when SIR2 is overexpressed. In a sir3 mutant strain the gene continues to be transcribed, even in SIR2 overexpressing conditions. In addition, treating the cells with nicotinamide counteracts the SIR2 overexpressing effect. Finally, conditions that are known to potentiate Sir2 deacetylation activity seem to mimic the effect of SIR2 overexpression on NHP6A. Our results suggest that Sir2 is involved in the regulation of NHP6A promoter, acting more as a specific repressor, rather than a long-range silencer. This effect is specific, and the Sir2 deacetylase activity is required for the Sir2 mediated repression of NHP6A. Moreover, the presence of the SIR complex seems required for Sir2 to silence NHP6A.

Increased cerebellar volume and BDNF level following quadrato motor training.

Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level.

Genetic remodeling and transcriptional remodeling of subtelomeric heterochromatin are different.

The structure, the extension, and the regulatory functions of telomeric and subtelomeric heterochromatin are not completely understood partly due to the difficulty of separating structural from functional features. We have previously observed that genetic alterations of telomeric heterochromatin components relieve transcriptional silencing. We have developed an analytical system allowing the separate determination of the effects of transcription and of genetic alterations on the subtelomeric structures. The uncoupled analysis, performed on the left extremity of chromosome III of Saccharomyces cerevisiae, consists of genetic dissections, induction of transcription of a resident gene, and chromatin analysis. The results allow (i) the determination of the precise localization and of the extension of heterochromatin (here from 0.9 to 2.6 kb from the innermost extremity of the C(1-3)A tract) and (ii) the definition of the transcription and of the genetically induced chromatin remodelings and of their marked differences, thus allowing (iii) specific analyses of the structural effects of the genetic modification of the heterochromatin components.