Background: Recent investigations have demonstrated a positive association between periodontitis and pregnancy complications. The purpose of this study was to determine the effect of periodontitis and the subgingival microbial composition on preeclampsia.Methods: A case-control study was carried out in Cali, Colombia that included 130 preeclamptic and 243 nonpreeclamptic women between 26 to 36 weeks of pregnancy. Sociodemographic data, obstetric risk factors, periodontal status, and subgingival microbial composition were determined in both groups. Preeclampsia was defined as blood pressure ‡140/90 mm Hg, and ‡2+ proteinuria, confirmed by 0.3 g proteinuria/24 hours of urine specimens. Controls were healthy pregnant women. Odds ratios (ORs) for periodontitis and subgingival microbiota compositions were calculated.Results: A total of 83 out of 130 preeclamptic women (63.8%) and 89 out of 243 controls (36.6%) had chronic periodontitis (OR: 3.0; 95% confidence interval (CI): 1.91 to 4.87; P <0.001). Clinical attachment loss increased in the case group (4.0 -0.10 mm) compared to the control group (3.0 -0.08 mm) (P <0.001). The average newborn birth weight from preeclamptic mothers was 2.453 g, whereas in controls was 2.981 g (P <0.001). Two red complex microorganisms, Porphyromonas gingivalis and Tannerella forsythensis, and the green complex microorganism Eikenella corrodens were more prevalent in the preeclamptic group than in controls (P <0.01).Conclusions: Chronic periodontal disease and the presence of P. gingivalis, T. forsythensis, and E. corrodens were significantly associated with preeclampsia in pregnant women. Further research is needed to establish pathogenic mechanisms of active periodontal disease and subgingival periodontopathogens related to preeclampsia development.

Rett Syndrome is a neurodevelopmental disorder typically caused by mutations in Methyl-CpG-Binding Protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms (ECGs) in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), indicating a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2Null/Y, also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2Null/+, show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally-mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, β-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2Null/Y mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2Null/Y mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2Null/Y mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current in order to prevent lethal cardiac arrhythmias.

Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.DOI: http://dx.doi.org/10.7554/eLife.14199.001