Autistic-like traits in laboratory rodents exposed to phthalic acid esters during early development - an animal model of autism?

Phthalates are chemical substances that are widely used to provide flexibility and durability to plastic materials. They leach from products in which they are mixed and reach living organisms. Results from experimental studies suggest that exposure to phthalates can have a negative impact on an individual's neuronal system and behavior. In this regard, exposure during early ontogenesis seems to be particularly dangerous due to the extensive growth and development of body structures and functions. Disruption during this critical time can result in alterations of behavior and the emergence of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Various animal models have been used to elucidate the pathogenesis of this disease. They are fundamental for research, and although the translation of results to humans is difficult, new animal models are being developed. The aim of this review is to summarize laboratory rodent studies in which early developmental phthalate exposure resulted in brain alterations and autistic-like behavioral traits. We also discuss the possibility of using early developmental phthalate exposure in rodents to create a new animal model of autism.

Impact of prenatal hypoxia on the development and behavior of the rat offspring.

The healthy development of the fetus depends on the exact course of pregnancy and delivery. Therefore, prenatal hypoxia remains between the greatest threats to the developing fetus. Our study aimed to assess the impact of prenatal hypoxia on postnatal development and behavior of the rats, whose mothers were exposed to hypoxia (10.5 % O2) during a critical period of brain development on GD20 for 12 h. This prenatal insult resulted in a delay of sensorimotor development of hypoxic pups compared to the control group. Hypoxic pups also had lowered postnatal weight which in males persisted up to adulthood. In adulthood, hypoxic males showed anxiety-like behavior in the OF, higher sucrose preference, and lower levels of grimace scale (reflecting the degree of negative emotions) in the immobilization chamber compared to the control group. Moreover, hypoxic animals showed hyperactivity in EPM and LD tests, and hypoxic females had reduced sociability compared to the control group. In conclusion, our results indicate a possible relationship between prenatal hypoxia and changes in sociability, activity, and impaired emotion regulation in ADHD, ASD, or anxiety disorders. The fact that changes in observed parameters are manifested mostly in males confirms that male sex is more sensitive to prenatal insults.

A mixture of diethylhexyl, diisononyl and dibutyl phthalate decreased anogenital distance, postnatal testosterone levels, and changed social behavior in Wistar rats.

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

Effectiveness of the antegrade colonic enema stopper at preventing stomal stenosis: long-term follow-up.

AIM OF THE STUDY: Stomal stenosis is the commonest complication of the antegrade colonic enema (ACE) procedure, reportedly occurring in 25-55% of patients. As such, a simple ACE stopper device (a small silicone plug sited in the ACE conduit between catheterisations) was designed to prevent stenosis. We performed a long-term follow-up study to determine the effectiveness of the stopper device. METHODS: A retrospective case note review was performed of all patients who successfully underwent a primary ACE procedure over an 8.5-year period (January 2002 to June 2010). The inclusion criteria were (i) a minimum of 6 months follow-up, (ii) simple appendicostomy, (iii) caecal/colonic flap. In all patients an ACE stopper was sited in the conduit for at least 4 months and removed only for catheterisation. Data are mean±SEM. MAIN RESULTS: 38 children were included in our study. Mean age at surgery was 9.6±0.5 years. Surgery was performed in 22 patients for incontinence and in 16 for chronic constipation. 31 underwent an appendicostomy and 7 had a caecal/colonic flap; all received an ACE stopper. The mean follow-up was 2.6±0.3 years. Only 3 patients (8%) developed stomal stenosis. The first occurred 6 months postoperatively, resulting from an ACE stopper which was too small and consequently persistently fell out. This conduit required dilatation. The second occurred at 27 months secondary to a stomal infection and required surgical revision. The third occurred 8 months postoperatively for no obvious cause, and was treated with dilation. 1 patient experienced stomal leakage. CONCLUSION: The ACE stopper is a simple yet highly effective method of preventing stomal stenosis. We recommend using the stopper in all ACE patients.