Autism as the Low-Fitness Extreme of a Parentally Selected Fitness Indicator

Siblings compete for parental care and feeding, while parents must allocate scarce resources to those offspring most likely to survive and reproduce. This could cause offspring to evolve traits that advertise health, and thereby attract parental resources. For example, experimental evidence suggests that bright orange filaments covering the heads of North American coot chicks may have evolved for this fitness-advertising purpose. Could any human mental disorders be the equivalent of dull filaments in coot chicks—low-fitness extremes of mental abilities that evolved as fitness indicators? One possibility is autism. Suppose that the ability of very young children to charm their parents evolved as a parentally selected fitness indicator. Young children would vary greatly in their ability to charm parents, that variation would correlate with underlying fitness, and autism could be the low-fitness extreme of this variation. This view explains many seemingly disparate facts about autism and leads to some surprising and testable predictions.     

Folic acid supplementation in pregnancy and implications in health and disease

Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies.     

Methyl‐CpG‐binding protein 2 polymorphisms and vulnerability to autism

The methyl‐binding protein gene, MECP2, is a candidate for involvement in autism through its implication as a major causative factor in Rett syndrome that has similarities to autism. Rare mutations in MECP2 have also been identified in autistic individuals. We have examined the possible broader involvement of MECP2 as a predisposing factor in the disorder. Analysis of polymorphic markers spanning the gene and comprising both microsatellites and single nucleotide polymorphisms (SNPs) by the transmission disequilibrium test in two collections of families (219 in total), one in the USA and one in the UK, has provided evidence for significant association (P = 0.009) for a three‐marker SNP haplotype of MECP2 with autism/autism spectrum disorders. This association is supported by association of both Single Sequence Repeat (SSR) and SNP single markers located at the 3′ end of the MECP2 locus and flanking sequence, the most significant being that of an indel marker located in intron 2 (P = 0.001 – Bonferroni corrected P = 0.006). This suggests that one or more functional variants of MECP2 existing at significant frequencies in the population may confer increased risk of autism/autism spectrum disorders and warrants further investigation in additional independent samples.     

Assessment of Techniques for Teaching School Children with Autism

BackgroundIn the modern era, researchers are facing a big challenge in diagnosing autism disorders. According to the Center for Disease Control and Prevention 2014 report, the prevalence of autism among children in the United States is approximately 1 out of 88 children; whereas, in South Korea, the prevalence is 1 out of 38. In India, most of the children with autism are yet to be diagnosed partly due to the lack of self-screening test compared to the other countries. Currently, no data is available for analyzing the prevalence of autism in India. In order to improve the behavior, the social interaction, and the verbal communication of these children, scientists are using various kinds of teaching methods.ObjectivesThe objectives of this work were to screen the level of autism among school children using Gilliam Autism Rating Scale (GARS-2) questionnaire and evaluate the effects of various teaching methods on social behavior of school children with autism.Methods and resultsNinety children in the age group between 3 – 16 years from three schools (S1 – 30, S2 – 30 and S3 – 30) with autism are participated in this study. In S1, the autistic children are trained with horseback riding and yoga therapy; whereas in the S2, the children are trained with normal teaching using blackboard and in the S3, the children are trained with cue cards. The GARS-2 questionnaire was used for assessing the communication, the stereotype behavior and the social interaction with the help of parents or the caregivers.ConclusionResults of our study revealed that raw and the standard scores of stereotyped behaviors was notably (p<0.05) low in S1 school children when collated with the other two (S2 and S3) schools. Similarly, the raw and the standard score of communication, the socially interaction sub-score was notably (p<0.05) low for the children in S3 when collated with the children in the other two schools. The study concluded that the horseback riding, the yoga therapy and the cue cards-based teaching methods improve the stereotyped behavior, increase concentration power and also helps in maintaining the children's mind stability.     

Loss of all three APP family members during development impairs synaptic function and plasticity,disrupts learning,and causes an autism‐like phenotype

The key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11.5 onwards. NexCre cTKO mice showed altered brain morphology with agenesis of the corpus callosum and disrupted hippocampal lamination. Further, NexCre cTKOs revealed reduced basal synaptic transmission and drastically reduced long‐term potentiation that was associated with reduced dendritic length and reduced spine density of pyramidal cells. With regard to behavior, lack of the APP family leads not only to severe impairments in a panel of tests for learning and memory, but also to an autism‐like phenotype including repetitive rearing and climbing, impaired social communication, and deficits in social interaction. Together, our study identifies essential functions of the APP family during development, for normal hippocampal function and circuits important for learning and social behavior.     

Transgenerational effects of prenatal bisphenol A on social recognition

Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders.     

Shifts in Ribosome Engagement Impact Key Gene Sets in Neurodevelopment and Ubiquitination in Rett Syndrome

1. Download : Download high-res image (226KB)
2. Download : Download full-size image

     

A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation

1. Download : Download high-res image (174KB)
2. Download : Download full-size image