UNASSIGNED: Hereditary neurodevelopmental disorders (NDDs) are prevalent in poorly prognostic pediatric diseases, but the pathogenesis of NDDs is still unclear. Irregular myelination could be one of the possible causes of NDDs.
UNASSIGNED: Here, whole exome sequencing was carried out for a consanguineous Pakistani family with NDDs to identify disease-associated variants. The co-segregation of candidate variants in the family was validated using Sanger sequencing. The potential impact of the gene on NDDs has been supported by conservation analysis, protein prediction, and expression analysis. A novel homozygous variant DOP1A(NM_001385863.1):c.2561A>G was identified. It was concluded that the missense variant might affect the protein-protein binding sites of the critical MEC interaction region of DOP1A, and DOP1A-MON2 may cause stability deficits in Golgi-endosome protein traffic. Proteolipid protein (PLP) and myelin-associate glycoprotein (MAG) could be targets of the DOP1A-MON2 Golgi-endosome traffic complex, especially during the fetal stage and the early developmental stages. This further supports the perspective that disorganized myelinogenesis due to congenital DOP1A deficiency might cause neurodevelopmental disorders (NDDs).
UNASSIGNED: Our case study revealed the potential pathway of myelinogenesis-relevant NDDs and identified DOP1A as a potential NDDs-relevant gene in humans.

The potential neurotoxic impact of anaesthetic agents has been the subject of sustained debate and continuing research. White matter, which comprises more than half of the brain volume and largely consists of myelinated axonal bundles, is critical for communication between diverse brain regions and for supporting neurobehavioural function. Evidence points to a correlation between exposure to anaesthesia and white matter alterations, which might underpin the ensuing cognitive and behavioural abnormalities. This review summarises the neuropathological and neuroimaging findings related to anaesthesia-induced white matter alterations in the developing brain. Future research is required to understand the effects of anaesthesia exposure on white matter development.

Consumption of cannabis is on the rise as public opinion trends toward acceptance and its consequent legalization. Specifically, the senior population is one of the demographics increasing their use of cannabis the fastest, but research aimed at understanding cannabis\' impact on the aged brain is still scarce. Aging is characterized by many brain changes that slowly alter cognitive ability. One process that is greatly impacted during aging is axonal myelination. The slow degradation and loss of myelin (i.e., demyelination) in the brain with age has been shown to associate with cognitive decline and, furthermore, is a common characteristic of numerous neurological diseases experienced in aging. It is currently not known what causes this age-dependent degradation, but it is likely due to numerous confounding factors (i.e., heightened inflammation, reduced blood flow, cellular senescence) that impact the many cells responsible for maintaining overall homeostasis and myelin integrity. Importantly, animal studies using non-human primates and rodents have also revealed demyelination with age, providing a reliable model for researchers to try and understand the cellular mechanisms at play. In rodents, cannabis was recently shown to modulate the myelination process. Furthermore, studies looking at the direct modulatory impact cannabis has on microglia, astrocytes and oligodendrocyte lineage cells hint at potential mechanisms to prevent some of the more damaging activities performed by these cells that contribute to demyelination in aging. However, research focusing on how cannabis impacts myelination in the aged brain is lacking. Therefore, this review will explore the evidence thus far accumulated to show how cannabis impacts myelination and will extrapolate what this knowledge may mean for the aged brain.

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.

A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.

This article\'s primary goal is to provide an image-based review to paediatricians to gain insight into the typical appearance of myelin evolution. We briefly discuss the structure and development of myelination, the role of qualitative and quantitative MRI in myelin imaging, and provide an image-based review as a quick reference for understanding the pattern of myelination on MR imaging.

White matter makes up about fifty percent of the human brain. Maturation of white matter accompanies biological development and undergoes the most dramatic changes during childhood and adolescence. Despite the advances in neuroimaging techniques, controversy concerning spatial, and temporal patterns of myelination, as well as the degree to which the microstructural characteristics of white matter can vary in a healthy brain as a function of age, gender and cognitive abilities still exists. In a selective review we describe methods of assessing myelination and evaluate effects of age and gender in nine major fiber tracts, highlighting their role in higher-order cognitive functions. Our findings suggests that myelination indices vary by age, fiber tract, and hemisphere. Effects of gender were also identified, although some attribute differences to methodological factors or social and learning opportunities. Findings point to further directions of research that will improve our understanding of the complex myelination-behavior relation across development that may have implications for educational and clinical practice.

Already during the last trimester of gestation, functional responses are recorded in foetuses and preterm newborns, attesting an already complex cerebral architecture. Then throughout childhood, anatomical connections are further refined but at different rates and over asynchronous periods across functional networks. Concurrently, infants gradually achieve new psychomotor and cognitive skills. Only the recent use of non-invasive techniques such as magnetic resonance imaging (MRI) and magneto- and electroencephalography (M/EEG) has opened the possibility to understand the relationships between brain maturation and skills development in vivo. In this review, we describe how these techniques have been applied to study the white matter maturation. At the structural level, the early architecture and myelination of bundles have been assessed with diffusion and relaxometry MRI, recently integrated in multi-compartment models and multi-parametric approaches. Nevertheless, technical limitations prevent us to map major developmental mechanisms such as fibers growth and pruning, and the progressive maturation at the bundle scale in case of mixing trajectories. At the functional level, M/EEG have been used to record different visual, somatosensory and auditory evoked responses. Because the conduction velocity of neural impulses increases with the myelination of connections, major changes in the components latency are observed throughout development. But so far, only a few studies have related structural and functional markers of white matter myelination. Such multi-modal approaches will be a major challenge in future research, not only to understand normal development, but also to characterize early mechanisms of pathologies and the influence of fetal and perinatal interventions on later outcome.

Fluctuations in gray and white matter volumes in addition to the fibers\' reorganization and refinement of synaptic connectivity apparently happen in a particular temporo-spatial sequence during the dynamic and prolonged process of cerebral maturation. These developmental events are associated with regional modifications of brain tissues and neural circuits, contributing to networks\' specialization and enhanced cognitive processing. According to several studies, improvements in cognitive processes are possibly myelin-dependent and associated to white matter maturation. Of particular interest is the developmental pattern of the prefrontal cortex (PFC), more specifically the PFC white matter, due to its role in high-level executive processes such as attention, working memory and inhibitory control. A systematic review of the literature was conducted using the Web of Science, PubMed and Embase databases to analyze the development of PFC white matter using Diffusion Tensor Imaging (DTI), a widely used non-invasive technique to assess white matter maturation. Both the research and reporting of results were based on Cochrane\'s recommendations and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Information extracted from 27 published studies revealed an increased myelination, organization and integrity of frontal white matter with age, as revealed by DTI indexes (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD] and axial diffusivity [AD]). These patterns highlight the extended developmental course of the frontal structural connectivity, which parallels the improvements in higher-level cognitive functions observed between adolescence and early adulthood.

Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5-3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice-Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury.