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

Two Distinct Nucleosome Alterations Characterize Chromatin Remodeling at the Saccharomyces cerevisiae ADH2Promoter

Glucose depletion derepresses the Saccharomyces cerevisiae ADH2 gene; this metabolic change is accompanied by chromatin structural modifications in the promoter region. We show that the ADR6/SWI1 gene is not necessary for derepression of the wild type chromosomal ADH2, whereas the transcription factor Adr1p, which regulates several S. cerevisiae functions, plays a major role in driving nucleosome reconfiguration and ADH2 expression. When we tested the effect of individual domains of the regulatory protein Adr1p on the chromatin structure of ADH2, a remodeling consisting of at least two steps was observed. Adr1p derivatives were analyzed in derepressing conditions, showing that the Adr1p DNA binding domain alone causes an alteration in chromatin organization in the absence of transcription. This alteration differs from the remodeling observed in the presence of the Adr1p activation domain when the promoter is transcriptionally active

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-basedMBP, 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

Poly(ADP-Ribosyl)ation Affects Histone Acetylation and Transcription

Poly(ADP-ribosyl) ation (PARylation) is a posttranslational protein modification catalyzed by members of the poly(ADP-ribose) polymerase (PARP) enzyme family. PARylation regulates a wide variety of biological processes in most eukaryotic cells including energy metabolism and cell death, maintenance of genomic stability, chromatin structure and transcription. Inside the nucleus, cross-talk between PARylation and other epigenetic modifications, such as DNA and histone methylation, was already described. In the present work, using PJ34 or ABT888 to inhibit PARP activity or over-expressing poly(ADP-ribose) glycohydrolase (PARG),we show decrease of global histone H3 and H4 acetylation. This effect is accompanied by a reduction of the steady state mRNA level of p300, Pcaf, and Tnf alpha, but not of Dnmt1. Chromatin immunoprecipitation (ChIP) analyses, performed at the level of the Transcription Start Site (TSS) of these four genes, reveal that changes in histone acetylation are specific for each promoter. Finally, we demonstrate an increase of global deacetylase activity in nuclear extracts from cells treated with PJ34, whereas global acetyltransferase activity is not affected, suggesting a role for PARP in the inhibition of histone deacetylases. Taken together, these results show an important link between PARylation and histone acetylation regulated transcription

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

A translational signature for nucleosome positioning in vivo

In vivo nucleosomes often occupy well-defined preferred positions on genomic DNA. An important question is to what extent these preferred positions are directly encoded by the DNA sequence itself. We derive here from in vivo positions, accurately mapped by partial micrococcal nuclease digestion, a translational positioning signal that identifies the approximate midpoint of DNA bound by a histone octamer. This midpoint is, on average, highly A/T rich (∼73%) and, in particular, the dinucleotide TpA occurs preferentially at this and other outward-facing minor grooves. We conclude that in this set of sequences the sequence code for DNA bending and nucleosome positioning differs from the other described sets and we suggest that the enrichment of AT-containing dinucleotides at the centre is required for local untwisting. We show that this signature is preferentially associated with nucleosomes flanking promoter regions and suggest that it contributes to the establishment of gene-specific nucleosome arrays

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

The molecular side of Quadrato Motor Training: implications for mental health

Neurotrophins are closely related to stress, mental health and well-being. Initially synthesized as precursor proteins (proneurotrophins), they can influence both developing and mature neural circuits. For example, while pro Brain-Derived Neurotrophic Factor (proBDNF) and Nerve Growth Factor (NGF) are related to learning and neuronal plasticity, proNGF is related to nociception and neuro-degeneration. Levels of pro-neurotrophins are considerably changed in neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. In addition, stress was shown to suppress BDNF synthesis and exogenous administration of BDNF may produce an opposing response in some cases, emphasizing the importance of activating the body’s own resources. To this aim, we utilized the Quadrato Motor Training (QMT), a specifically-structured sensorimotor training, which was found to increase alpha synchronization and improve spatial cognition, reflectivity, creativity, as well as emotion regulation and general selfefficacy. Our studies demonstrated that proNGF and proBDNF vary following several weeks of QMT practice and are correlated with improved creativity, which is closely related to mental well-being. Together, these results support the idea that QMT is a useful integrated training that may aid in enhancing physical and mental well-being. In the current talk, we will discuss the implications of combining cognitively challenging physical training for healthy development and aging