3D genome organization in the central nervous system,implications for neuropsychological disorders

Chromosomes in eukaryotic cell nuclei are highly compacted and finely organized into hierarchical threedimensional(3 D) configuration. In recent years, scientists have gained deeper understandings of 3 D genome structures and revealed novel evidence linking 3 D genome organization to various important cell events on the molecular level. Most importantly, alteration of 3 D genome architecture has emerged as an intriguing higher order mechanism that connects disease-related genetic variants in multiple heterogenous and polygenic neuropsychological disorders, delivering novel insights into the etiology. In this review, we provide a brief overview of the hierarchical structures of 3 D genome and two proposed regulatory models,loop extrusion and phase separation. We then focus on recent Hi-C data in the central nervous system and discuss 3 D genome alterations during normal brain development and in mature neurons. Most importantly,we make a comprehensive review on current knowledge and discuss the role of 3 D genome in multiple neuropsychological disorders, including schizophrenia, repeat expansion disorders, 22 q11 deletion syndrome, and others.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance

Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveillance.Methods All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules(GDS).Spearman’s correlation coefficients and Kappa values were obtained.Taking GDS as a reference assessment,the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic(ROC)curves.The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule,Second Edition(ADOS-2).Results In total,150 children aged 12–42 months with ASD were enrolled.The developmental quotients of the CNBS-R2016 were correlated with those of the GDS(r=0.62–0.94).The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays(Kappa=0.73–0.89),except for Fine Motor.There was a significant difference between the proportions of Fine Motor,delays detected by the CNBS-R2016 and GDS(86.0%vs.77.3%).With GDS as a standard,the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor,which was 0.70.In addition,the positive rate of ASD was 100.0%and 93.5%when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used,respectively.Conclusion The CNBS-R2016 performed well in developmental assessment and screening for children with ASD,especially by Communication Warning Behaviors subscale.Therefore,the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Neuropsychological and Social Outcome of Patients Sustaining Traumatic Brain Injury in Cotonou

This inaugural study in Benin was aimed at assessing neuropsychological and behavioural problems of patients with traumatic brain injury managed at the Hubert Koutoukou Maga Teaching hospital in Cotonou, and the impact on their standard of leaving. This was a prospective and cross-cutting study with a descriptive and analytical aim. It was carried out from 1 July to 30 October 2018. The study population included patients over 15 years of age who had experienced TBI. A purposive sampling of 585 patients with TBI was done, of which 142 patients could not be reached by phone while. The mean age of patients was 37.16 ± 13.9 years, with extremes ranging from 16 to 87 years. The most frequent complaints were behavioural disorder (79.5%), headache (63.8%) and memory loss (50.4%). The average duration of post traumatic amnesia was 9.08 ± 38.56 days. Sixty-three patients (68.5%) had post-traumatic amnesia that lasted less than 30 minutes and 25 patients (19.2%) had post-traumatic amnesia that lasted over a month. Neuropsychological disorders were more frequent in patients with severe TBI. Attention disorders and difficulties in elaborating strategies were noticed without any statistically significant difference in mild, moderate as well as severe TBI. Nineteen patients lost their job, thus raising the unemployment rate in our sample from 6% to 21%. Among the 100 patients (75%) that recovered their job, 14% had medical follow-up and 10% returned to part-time work. Salary remained unchanged for 61.2% of TBI patients.

Cognitive Impairment and Recovery in Meningiomas and Low-Grade Gliomas

This study aims to elucidate the nature of cognitive deficits caused by intracranial tumors, as well as to examine how a surgical operation of the tumor may affect tumor-induced cognitive deficits. The patient group included 43 individuals with meningioma or low-grade glioma admitted to a surgical operation of the tumor. Neuropsychological examination was conducted preoperatively, as well as three and 12 months postoperatively. The control group comprised 31 healthy subjects. In the tumor patients, preoperative cognitive performance was compromised in several cognitive domains as compared to the controls. The tumor patients with frontal and large tumors showed impairment virtually across all cognitive domains. Postoperatively, the cognitive performance of the meningioma and the small tumor group improved in all domains, with the performance of the low-grade glioma group and the large tumor group reflecting more modest cognitive improvement. Most of this improvement did not emerge until the 12 months follow-up. Cognitive impairment due to an intracranial tumor is diffuse affecting most cognitive domains. Cognitive recovery after the surgery is more noticeable in patients with meningiomas and small tumors, and the recovery will require a minimum of one year time-wise. This evidence is of significant value when planning both clinical treatment and rehabilitation of intracranial tumor patients.

Clinical significance of germline copy number variation in susceptibility of human diseases

Germline copy number variation （CNV） is considered to be an important form of human genetic poly- morphisms. Previous studies have identified amounts of CNVs in human genome by advanced technologies, such as comparative genomic hybridization, single nucleotide genotyping, and high-throughput sequencing. CNV is speculated to be derived from multiple mechanisms, such as nonallelic homologous recombination （NAHR） and nonhomologous end-joining （NHEJ）. CNVs cover a much larger genome scale than single nucleotide polymorphisms （SNPs）, and may alter gene expression levels by means of gene dosage, gene fusion, gene disruption, and long-range regulation effects, thus affecting individual phenotypes and playing crucial roles in human pathogenesis. The number of studies linking CNVs with common complex diseases has increased dramatically in recent years. Here, we provide a comprehensive review of the current understanding ofgermline CNVs, and summarize the association of germline CNVs with the susceptibility to a wide variety of human diseases that were identified in recent years. We also propose potential issues that should be addressed in future studies.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.