Prenatal Trimethyltin Exposure Induces Long-Term DNA Methylation Changes in the Male Mouse Hippocampus.

Trimethyltin (TMT) is an irreversible neurotoxicant. Because prenatal TMT exposure has been reported to induce behavioral changes, this study was conducted to observe gender differences and epigenetic changes using a mouse model. In behavioral testing of offspring at 5 weeks of age, the total times spent in the center, corner, or border zones in the male prenatal TMT-exposed mice were less than those of control unexposed mice in the open-field test. Female TMT-exposed mice scored lower on total numbers of arm entries and percentages of alternations than controls in the Y-maze test with lower body weight. We found that only TMT-exposed males had fewer copies of mtDNA in the hippocampus and prefrontal cortex region than controls. Additional epigenetic changes, including increased 5-methyl cytosine/5-hydroxymethyl cytosine levels in the male TMT hippocampus, were observed. After methylation binding domain (MBD) sequencing, multiple signaling pathways related to metabolism and neurodevelopment, including FoxO signaling, were identified by pathway analysis for differentially methylated regions (DMRs). Increased FOXO3 and decreased ASCL1 expression were also observed in male TMT hippocampi. This study suggests that sex differences and epigenetics should be more carefully considered in prenatal toxicology studies.

Effect of Gait Training Program with Mechanical Exoskeleton on Body Composition of Paraplegics.

PURPOSE: To identify the effect of a 52-weeks gait training program with an exoskeletal body-powered gait orthosis on the body composition of paraplegics. PATIENTS AND METHODS: Ten subjects with spinal cord injury at the thoracolumbar spine level for more than 2 years participated and were divided into exercise (n=5) and nonexercise (n=5) groups. A gait training program comprising stages 1-6 with customized exoskeletal body-powered gait orthosis was conducted for 52-weeks. A six-stage gait training program was conducted to manage the body composition and prevent obesity, and the changes in the body composition before and after the program were determined through bioelectrical impedance analysis. RESULTS: No significant changes in weight, fat-free mass (kg), lean body mass (kg), and percent fat mass (%) are seen in the exercise group before and after the 52-weeks program. However, fat-free mass (pre = 47.3± 6.5, post = 44.3 ± 5.4, kg), lean body mass (pre = 45.2 ± 6.3, post = 42.3±5.2, kg), and percent fat mass (pre = 30.1 ± 12.1, post = 40.9 ± 9.1, kg) show significant changes (p < 0.05) in the nonexercise group. In the nonexercise group, among lean body mass changes over 52-weeks in the upper limbs (-31%), trunks (-9.7%), and lower limbs (-8.6%), upper limbs exhibit the most significant decrease (p < 0.05). CONCLUSION: The gait training program with exoskeletal body-powered gait orthosis has a positive effect on fat management in the whole body and lean body mass loss in paraplegics. Furthermore, it is effective in preventing continuous muscle loss and in maintaining health by reducing body fat. Body composition measurements with bioelectrical impedance analysis for paraplegics can be applied in various clinical areas and can be combined with various arbitration methods such as rehabilitation program.

Acute Valproate Exposure Induces Sex-Specific Changes in Steroid Hormone Metabolism in the Cerebral Cortex of Juvenile Mice.

Valproic acid (VPA), an antiepileptic and mood stabilizer, modulates neurotransmission and gene expression by inhibiting histone deacetylase activity. It is reported that VPA may affects the steroid hormone level. In this study, VPA-induced acute metabolic alterations were investigated using liquid chromatography-tandem mass spectrometry in prepubertal mice brain. In VPA-treated (400 mg/kg in saline solution, intraperitoneal) mice, cortisol levels were increased (female: P < 0.004, male: P < 0.003) and 17ß-estradiol levels were decreased (Both P < 0.03). Furthermore, in the VPA-treated male mice, dihydrotestosterone levels were increased (P < 0.02) and testosterone were decreased (P < 0.002). The 4-hydroxylase activity was upregulated in the female VPA-treated mice (P < 0.01) and the 5α-reductase activity was increased in the male VPA-treated mice (P < 0.003). These results indicate sex specific differences in VPA-induced steroid metabolism in the brain cortex.

Evaluation of Calf Muscular Function During the Recovery Phase After the Repair of an Achilles Tendon Rupture.

Background: During the recovery phase after the repair of an Achilles tendon rupture, measuring calf muscular function is important for predicting prognosis. Tensiomyography (TMG) is a selective and non-invasive diagnostic method for skeletal muscular contractile properties based on the displacement of the muscle belly. Case Presentation: Tensiomyography gives information about maximal displacement of the muscle belly (Dm), delay time, contraction time (Tc), sustain time, and relaxation time. Using Tensiomyography we evaluated a patient that had Achilles tendon rupture surgery. The contralateral normal side measurements were also performed for evaluation and comparison of the site of injury. Findings: In this study, the maximal displacement of the muscle belly changed significantly compared to other parameters. The maximal displacement of the muscle belly decreased after cast removal day and increased gradually during the early recovery phase and then slightly decreased again during the late recovery phase. Conclusions: These responses of the maximal displacement of muscle belly show a correlation with the recovery of muscular function.