Myelination, the process of forming a myelin sheath around nerve fibers, is critical not only during early development but also throughout adulthood. This article explores the multifaceted impacts of myelination on the adult brain, highlighting its importance in cognitive functions, neurological health, and overall brain efficiency. In adults, efficient myelination enhances information processing speed, supports memory consolidation, and contributes to cognitive reserve, potentially delaying the onset of neurodegenerative diseases. Myelination ensures synchronized neural activity and energy-efficient brain function, playing a key role in complex cognitive tasks and coordination. Despite a slower rate of plasticity compared to early development, the adult brain retains the ability to adapt and learn, with myelination facilitating these processes. This article also draws parallels between myelination in the brain and learning curves in deep learning Perceptrons, emphasizing how reduced stimulation and experience can significantly slow down cognitive and learning processes. Additionally, the clinical implications of myelination are discussed, including its role in multiple sclerosis and age-related cognitive decline, along with strategies to maintain and enhance myelin health through lifestyle choices and emerging pharmacological interventions. Understanding the ongoing significance of myelination in the adult brain, and its comparison to artificial neural networks, is crucial for developing interventions to support cognitive health and mitigate neurological disorders.

(1) Background: Substantial evidence that neural timing deficits are prevalent in developmental disorders, aging, and concussions resulting from a mild Traumatic Brain Injury (mTBI) is presented. We show that if timing deficits are remediated using low-level movement discrimination training, then high-level cognitive skills, including reading, attention, processing speed, and working memory improve substantially. (2) Methods: Two case studies are presented using MEG source imaging on an adult dyslexic, and a healthy older adult observed before and after training on movement discrimination two times/week for 8 weeks for adult dyslexic. (3) Results: We found improvements in reading, attention, processing speed, and working memory on neuropsychological tests. Substantial MEG signal increases in visual Motion Networks (V1, V3, MT, MST), Attention Networks (ACC, dlPFC, vlPFC and precuneous/ PCC areas) and Memory Networks (dlPFC). (4) Conclusions: Improving neural timing deficits before cognitive exercises to improve specific cognitive skills provides a rapid and effective method to improve cognitive skills. Improving the timing and sensitivity of low-level dorsal pathways, improving feedforward and feedback pathways, is essential to improve high-level cognitive skills. This adaptive training with substantial feedback shows cognitive transfer to tasks not trained on, significantly improving a person’s quality of life rapidly and effectively.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception, in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Abstract: Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to addressing the urgent need for practical solutions to the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

The synuclein family consists of α-, β-, and γ-Synuclein (α-Syn, β-Syn, and γ-Syn), expressed in the neurons and concentrated in synaptic terminals. While α-Syn is at the center of interest due to its implication in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, limited information exists on the other members. The current study aimed at investigating the biological role of γ-Syn controlling the midbrain dopamine (DA) function. We generated two different mouse models with i) γ-Syn overexpression induced by an adeno-associated viral vector and ii) γ-Syn knockdown induced by a ligand-conjugated antisense oligonucleotide, to modify the endogenous γ-Syn transcription levels in midbrain DA neurons. The progressive overexpression of γ-Syn decreased DA neurotransmission in the nigrostriatal and mesocortical pathways. In parallel, mice evoked motor deficits in the rotarod and impaired cognitive performance as assessed by novel object recognition, passive avoidance, and Morris water maze tests. Conversely, acute γ-Syn knockdown selectively in DA neurons facilitated forebrain DA neurotransmission. Importantly, modifications in γ-Syn expression did not induce the loss of DA neurons or changes in α-Syn expression. Collectively, our data strongly suggest that DA re-lease/re-uptake processes in the nigrostriatal and mesocortical pathways are partially dependent on SNc/VTA γ-Syn transcription levels, and are linked to modulation of DA transporter function, similar to α-Syn.

Land’s basic metric is soil organic carbon (SOC) yet global estimates range 1,417–15,000 Gt C. Erosion of ancient topsoil and loss of soil taxa are most urgent of all context-triage concerns, and most ignored. Re-evaluation of topographical terrain on a non-flat Earth increases most soil dynamic inventories. Carbon credits of our neglected and disappearing SOC stocks are enumerated for mineral soils (~4,100 Gt C plus ca. 20–30% glomalin), Permafrost (>4,200 Gt C), peat (1,123 Gt C), plant roots (916 Gt C), litter (600 Gt C), microbes (200 Gt C), fungi (30 Gt C), biocrust (10–20 Gt C), earthworms (2.3–3.6 Gt C), termites (0.15 Gt C), nematodes (0.06 Gt C), ants (0.024 Gt C), and soil viruses (0.02–4.0 Gt C). Net contribution to atmospheric CO₂ is more from biotic topsoil loss (>10 Gt C/yr) than fossil fuels (<10 Gt C/yr). Although higher CO₂ results in a terrestrial greening effect with Net Primary Productivity (NPP) now ~220 Gt C/yr (cf. ~20 Gt C/yr Ocean NPP), this is arguably offset by topsoil erosion, desert expansion, plus fire at net ~16–20 Gt C/yr lost due, in part, to extravagant meat-eating with unsupportable, humus-depleting farm management. In particular, excess synthetic Nitrogen acidifies topsoil and destroys the natural SOC biota. Review shows critical topsoil loss up to 20,000 tonnes per second and, when soil microbes/invertebrates are properly considered, extinctions as high as 23 taxa per second. Sustainable Development Goals (SDGs) fail without solid soil foundation. Rather, heritage farm-data points to resolution in organic husbandry. Remedy via natural vermi-compost, 100% organic farming and practical Permaculture is under a simple premise that the Problem (i.e., SOC loss) is the Solution (viz., SOC restoration).

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations include severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of depakoke are evocative of a mitochondrial etiology. However, the genotype-phenotype correlation remains undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provide evidence of a deficient oxidative phosphorylation pathway responsible for ATP synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis reveals metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirms the suspected mitochondrial etiology, as the proband’s mitochondria exhibit an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that sub-optimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward OXPHOS leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of fetal and postnatal brain.

Background: Social skills deficits are present in 43.3% of major depressed patients and significantly impact health-related quality of life. However, studies concerning social deficits as state-dependent markers of depression are limited. Objective: To delineate the effects of severity of depression, personality characteristics, family support satisfaction and self-esteem on social skills in clinical depression. Methods: We recruited 150 patients with major depressive disorder or persistent depressive disorder and assessed 1) Beck Depression Inventory-II (BDI-II), 2) Social Skill Inventory (SSI), 3) Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) Questionnaire 4) Rosenberg Self-Esteem Scale (RSES) and 5) Maudsley Personal Inventory (MPI). Results: Social skills deficits were significantly associated with female gender, age < 40 years, depression severity, introvert / neurotic personality, and lowered family support satisfaction and self-esteem. A large part of the variance (47.2%) in social skills deficits was predicted by satisfaction of family support, introvert personality, and low self-esteem. Exploratory Factor Analysis showed that a bifactorial model best fitted the data with a) a general factor loading highly on BDI-II, SSI emotional and social, APGAR, RSES, MPI_introvert and MPI_neurotic scores, and b) a single-group factor loading on both SSI, RSES, and MPI introvert scores. Conclusion: In clinical depression, social skills deficits covary with increasing severity of depression and thus constitute a state marker of depression, and independently from severity of depression covary with introvert personality features. As such, remission of social skills deficits may emerge as a novel objective for the treatment of depression and prevention of new episodes.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of laminin and collagen IV within the ECM of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. Results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats the pattern was broken into aggregated granule-like immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra-and ipsilateral side of the TBI rats. However, in TBI rats most of the muscles from the contralateral hindlimb showed a significant increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

Attention deficit hyperactivity disorder (ADHD) results in various functioning impairments in children’s lives and families. Parents of children with ADHD report high levels of parenting stress, low levels of parental self-efficacy and use of more authoritarian and/or permissive parenting practices than parents of typically developing children. Intervention programs need to address both children’s and parents’ needs and multimodal intervention programs could cover this demand. The aim of this study was to examine the efficacy of “Child ViReal Support Program” - a multi-level evidence-based comprehensive program - on parenting stress, parental self-efficacy, parenting practices, and the core symptoms of children’s ADHD. Families with a child diagnosed with ADHD (n = 16) were randomly allocated to two groups (PC and CP; P = parent training, C = child training) and a cross-over design was utilized. Participating parents completed, in four different times during the study, the Parenting Stress Index-Short Form, the Parenting Sense of Competence Scale, the Parenting Styles and Dimensions Questionnaire-Short Version and the parent form of the ADHD Rating Scale-IV. Parents from both groups, after their participation in the parent training, demonstrated reduced parenting stress, enhanced parental self-efficacy and increased the employ of democratic parenting practices. More than that, they reported decreased levels of inattention and impulsivity/hyperactivity for their children. Evidence-based multi-level intervention programs could produce positive effects in parents and children by incorporating effective methods and tools in accordance with the needs and the demands of the family context.