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[This corrects the article DOI: 10.1371/journal.pone.0183026.].

Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.

Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease.Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles.Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p

Previous work from our group and others utilizing animal models have demonstrated long lasting structural and functional alterations in the meso-cortico-striatal dopamine pathway following prenatal cocaine treatment. We have shown that prenatal cocaine treatment results in augmented D1 -induced cyclic AMP (cAMP) and cocaine-induced immediate-early gene expression in the striatum of adult mice. In this study we further examined basal as well as cocaine or D1-induced activation of a set of molecules known to be mediators of neuronal plasticity following psychostimulant treatment, with emphasis in the dorsal striatum (Str) and nucleus accumbens (NAc) of adult mice exposed to cocaine in utero. Basally, in the striatum of prenatal cocaine treated (PCOC) mice there were significantly higher levels of a number of the transcription factors studied. Following acute administration of cocaine (15 mg/kg, i.p.) or D1 agonist (SKF 82958; 1 mg/kg, i.p.) there were significantly higher levels of Ser133 P-CREB, Thr34 P-DARPP-32, and Thr202/Tyr204 P-ERK2 in the Str, that were significantly augmented in PCOC mice. In sharp contrast, in the NAc of those mice, we found increased P-CREB and P-ERK2 in PSAL mice, a response that was not evident in PCOC mice. Examination of Ser 845 P-GluA1 revealed increased levels in PSAL mice, but significantly decreased levels in PCOC mice in both the Str and NAc following acute administration of cocaine or D1 agonist. We also found significantly higher levels of the BDNF precursor, pro-BDNF and one of its receptors, TrkB in the Str of PCOC mice. These results suggest a persistent up-regulation of molecules critical to D1 and BDNF signaling in the Str of adult mice exposed to cocaine in utero. These molecular adaptations may underlie components of the behavioral deficits evident in exposed animals and a subset of exposed humans, and may represent a therapeutic target for ameliorating aspects of the prenatal cocaine-induced phenotype.