Long-lasting and Sex-dependent Effects of Postweaning Swimming Exercise on Social Dominance in Adult Mice.

Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. The purpose of this study was to investigate the potential effects of postweaning swimming exercise on social dominance and metabolic adaptation in adult mice. Three-week-old mice performed 1 h of swimming exercise in warm water for 4 weeks. A series of behavioral tests, such as the social dominance test (SDT), open field test (OFT), and forced swim test (FST), were conducted. Behavioral test results showed that both male and female mice in the swimming group had a higher rank than those in the sedentary group in the SDT of early adulthood, while only female mice in the swimming group maintained the social dominance in late adulthood. There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.

[Genetic and clinical analysis of a novel GLB1 gene variant in a Chinese patient with GM1-gangliosidosis].

OBJECTIVE: To explore the genotype-phenotype correlation of a case with GM1-gangliosidosis caused by compound heterogenic variants in GLB1. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Trio-based whole-exome sequencing (WES) was performed for the family and suspected mutation was verified by Sanger sequencing. RESULTS: The proband, a 2-year-3-month old Chinese girl, presented with psychomotor deterioration, absent speech, intellectual disabilities and behavior problem. Trio-based WES has identified compound heterozygosity for 2 variants in the GLB1 gene: NM_000404.2:c.1343A>T, p.Asp448Val and c.1064A>C, p.Gln355Pro (GRCh37/hg19),which was inherited from the mother and father, respectively. Homozygous or compound heterozygous pathogenic variants in GLB1, encoding ß-galactosidase, are responsible for GM1-gangliosidosis,an autosomal recessive lysosomal storage disorder characterized by variable degrees of neurodegeneration and skeletal abnormalities. The p.Asp448Val variant has been classified as pathogenic for GM1 gangliosidosis in medical literatures for the reason that functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable ß-galactosidase activity compared to wild type GLB1. The p.Gln355Pro variant has not been reported in literatures or database. The variant is highly conserved residue (PM1), and was not found in either the Genome Aggregation Database or the 1000 Genomes Project (PM2) and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3). Next, the ß-galactosidase activity of the patient's peripheral blood leukocytes was determined by fluorescent method. The result was 0.0 nmol/mg. It showed that the p.Gln355Pro variant also resulted in loss of ß-galactosidase activity, thus the variant was classified into clinical pathogenic variant. CONCLUSION: Our study expands the mutational spectrum of the GLB1 gene and provides genetic counseling for the family.

[Genetic and clinical analysis of KIF2A gene variant in a Chinese patient with complex cortical dysplasia and other brain malformations].

OBJECTIVE: To explore the genetic basis for a child featuring complex cortical dysplasia and other brain malformations (CDCBM3). METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out for the family trio. Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 1-year-and-2-month old Chinese boy, had presented with motor developmental delay, lissencephaly, severe cognitive impairments, absent speech and congenital laryngomalacia. WES revealed that he has harbored a heterozygous missense variant of the KIF2A gene, namely NM_001098511.2: c.952G>A, p.Gly318Arg (GRCh37/hg19). The highly conserved residue is located around the ATP nucleotide-binding pocket in the kinesin motor domain (PM1). The variant was not found in the Genome Aggregation Database and the 1000 Genomes Project (PM2), and was predicted to be deleterious on the gene product by multiple in silico prediction tools (PP3). This variant was unreported previously and was de novo in origin (PS2). Based on the ACMG guidelines, it was categorized as likely pathogenic (PS2+PM1+PM2+PP3). Furthermore, the congenital laryngomalacia found in our patient was absent in previously reported CDCBM3 cases. CONCLUSION: The novel variant of the KIF2A gene probably underlay the disorders in the proband. Above finding has expanded the phenotypic and mutational spectrum of CDCBM3.

Effects of chronic triclosan exposure on social behaviors in adult mice.

Triclosan (TCS), a newly identified environmental endocrine disruptor (EED) in household products, has been reported to have toxic effects on animals and humans. The effects of TCS exposure on individual social behaviors and the potential underlying mechanisms are still unknown. This study investigated the behavioral effects of 42-day exposure to TCS (0, 50, 100 mg/kg) in drinking water using the open field test (OFT), social dominance test (SDT), social interaction test (SIT), and novel object recognition task (NOR). Using 16S rRNA sequencing analysis and transmission electron microscopy (TEM), we observed the effects of TCS exposure on the gut microbiota and ultrastructure of hippocampal neurons and synapses. Behavioral results showed that chronic TCS exposure reduced the social dominance of male and female mice. TCS exposure also reduced social interaction in male mice and impaired memory formation in female mice. Analysis of the gut microbiota showed that TCS exposure increased the relative abundance of the Proteobacteria and Actinobacteria phyla in female mice. Ultrastructural analysis revealed that TCS exposure induced ultrastructural damage to hippocampal neurons and synapses. These findings suggest that TCS exposure may affect social behaviors, which may be caused by altered gut microbiota and impaired plasticity of hippocampal neurons and synapses.

[Analysis of clinical manifestation and a mosaic frameshift variant of the KMT2D gene in a Chinese patient with Kabuki syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene. METHODS: Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing. RESULTS: The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported. CONCLUSION: This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.

Repeated 3,3-Dimethyl-1-butanol exposure alters social dominance in adult mice.

The influence of gut microbiota on brain function and brain disorders has been attracted more and more attention. Trimethylamine N-oxide (TMAO), an indirect metabolite of gut microbiota, has been linked to aging, cognitive impairment, and other brain disorders. However, the relationship between TMAO and social behaviors are still poorly understood. Adult male mice were exposed to drinking water containing 3,3- Dimethyl-1-butanol (DMB), an indirect inhibitors of TMAO, for 21 continuous days followed by a series of behavioral tests to detect the effect of DMB exposure on social behaviors, mainly including social dominance test (SDT), bedding preference test (BP), sexual preference test (SP), social interaction test (SI), open field test (OFT), tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSF), and novel object recognition (NOR) task. In the SDT, compared with the control group, the mice treated with DMB (both 0.2% and 1.0%), both high-ranked and low-ranked mice, showed a reduction in the number of victories. There is no statistical difference on sexual preference, anxiety, depression-like behavior phenotype, and memory formation. In conclusion, the present findings provide direct evidence, for the first time, that repeated DMB exposure produces significant effects on social dominance of adult mice, without any effects on sexual preference, anxiety, depression-like behavior phenotype or memory formation, highlighting the regulatory effects of gut-brain interaction on social behaviors.

Change in an urban food environment within a single year: Considerations for food-environment research and community health.

Past research on food-environment change has been limited in key ways: (1) considering only select storefront businesses; (2) presuming items sold based on businesses category; (3) describing change only in ecological terms; (4) considering multi-year intervals. The current study addressed past limitations by: (1) considering a full range of both storefront and non-storefront businesses; (2) focusing on items actually offered (both healthful and less-healthful varieties); (3) describing individual-business-level changes (openings, closings, changes in offerings); (4) evaluating changes within a single year. Using a longitudinal, matched-pair comparison of 119 street segments in the Bronx, NY (October 2016-August 2017), investigators assessed all businesses-food stores, restaurants, other storefront businesses (OSBs), street vendors-for healthful and less-healthful food/drink offerings. Changes were described for individual businesses, individual street segments, and for the area overall. Overall, the number (and percentage) of businesses offering any food/drink increased from 45 (41.7%) in 2016 to 49 (45.8%) in 2017; businesses newly opening or newly offering food/drink cumulatively exceeded those shutting down or ceasing food/drink sales. In 2016, OSBs (gyms, barber shops, laundromats, furniture stores, gas stations, etc.) together with street vendors represented 20.0% and 27.3% of businesses offering healthful and less-healthful items, respectively; in 2017, the percentages were 31.0% and 37.0%. While the number of businesses offering healthful items increased, the number offering less-healthful items likewise increased and remained greater. If change in a full range of food/drink availability is not appreciated: food-environment studies may generate erroneous conclusions; communities may misdirect resources to address food-access disparities; and community residents may have increasing, but unrecognized, opportunities for unhealthful consumption.