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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T-maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism.
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PMID:Mouse behavioral assays relevant to the symptoms of autism. 1791 30

Sound nurture requires skills concerning nutrition and emotions, skills that are particularly important in key stages relating to brain development. We are recognizing more clearly the way that serious changes from our hunter-gatherer waterside lifestyle are affecting both our diet and our emotional relationships: first the changes a few hundred generations ago in the agricultural revolution: and more recently in the industrial revolution. These effects have been aggravated in the last century by excessively profit-driven intensive farming, and recently by intensive food-marketing--particularly to children. People are gradually becoming aware how very susceptible is the most vulnerable stage of the lifecycle, the reproductive phase. From long before fertilization and conception, parental nutrition affects a person's development and health for life. Controlled trials show marked effects of nurture on the brain's subsequent acuity. Brain structure throughout development has become visible through modern scans, and also brain activity and mental response. The neural tube, forming at around 3 weeks, if undernourished may be inadequately sealed and demarcated, leading to incomplete interconnection between brain regions. Results vary, but can emanate as: autism or attention-deficit/hyperactivity-disorder (AD/HD); difficulty with relationships and social sense; poor self-control, with risk of violence. Evidence indicates that over 80% of current reproductive hazards, including infertility and malformations, might be prevented purely by sound all-round nurture. Between the embryonic stage and adulthood the brain makes several developmental spurts. Particularly during these spurts, sound nutrition and activity help the brain reach its full genetic potential for capacity, acuity, and connections between regions. From the beginning, hormones and nutrients, or their deficits, are setting gene-switches for life. Good bonding and feeding sets gene-switches positively; shock, stress or poor nutrition, negatively. Forceps delivery combined with serious early separation, correlates with over 4 times the risk of criminal violence by the age of 18. So disruptions of nurture set at risk not only body and brain but a person's very spirituality. Understanding of the biochemistry and epigenetics highlights our urgent need to learn from our evolutionary ways, not only of childbearing, but of a physically active life nourished by foods from the water and the wild.
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PMID:Nurturing the brain nutritionally and emotionally from before conception to late adolescence. 1830 73

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/-) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/-) mated to VIP +/- males with the offspring of wild type (WT) mothers mated to VIP +/- males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze. These comparisons revealed few differences in general health among offspring of WT and VIP deficient mothers, and all offspring exhibited normal responses in fear conditioning and in the acquisition phase of spatial discrimination in the water maze. WT mothers produced offspring that were normal in all tests; the reduced VIP in their VIP +/- offspring apparently did not contribute to any defects in the measures under study. However, regardless of their own VIP genotype, all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in their male littermates, and the extent of their impairment was related to their own VIP genotype. This study has shown that intrauterine conditions had a greater influence on behavioral outcome than did genetic inheritance. In addition, the greater prevalence of deficits in social behavior and the resistance to change seen in reversal learning in the male offspring of VIP deficient mothers indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders such as autism.
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PMID:Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice. 1831 78

Methylmercury (MeHg) has cytotoxic effects on animals and humans, and a major target organ for MeHg is the central nervous system (CNS). It is well known that the developing CNS is extremely vulnerable to MeHg-induced changes in comparison to the mature brain. Most studies have concentrated on the direct effects of high levels of prenatal MeHg exposure. Surprisingly, behavioral outcomes found in adult offspring exposed developmentally to the neurotoxic effects of chronic, low-dose mercury more akin to ingestion in humans are not well characterized. The objective of this study was to determine whether such exposure produces deleterious effects on behavior in adult mice, including motor/coordination abilities, overall activity and mnemonic function. Developing mouse fetuses were exposed in utero during gestational days 8-18 by giving pregnant C57Bl/6J female mice food containing MeHg at a daily dose of 0.01 mg/kg body weight. Adult mice prenatally exposed to MeHg exhibited significant deficits in motor abilities, coordination, and overall activity, as measured by rotarod, footprint analysis and open field. In addition, MeHg-exposed mice were impaired with respect to reference memory but not in a visible, cued version of the Morris water maze task. These results indicate that prenatal exposure to the lowest dose of MeHg examined to date can have long-lasting motor and cognitive consequences on adult offspring. These findings have far reaching implications related to putative safe levels of MeHg ingestion, particularly during pregnancy, and increasing rates of cognitive and psychological disorders (e.g. attention hyperactivity deficit disorder, autism) in our society.
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PMID:Chronic, low-dose prenatal exposure to methylmercury impairs motor and mnemonic function in adult C57/B6 mice. 1843 14

Core symptoms of autism include deficits in social interaction, impaired communication, and restricted, repetitive behaviors. The repetitive behavior domain encompasses abnormal motoric stereotypy, an inflexible insistence on sameness, and resistance to change. In recent years, many genetic mouse models of autism and related disorders have been developed, based on candidate genes for disease susceptibility. The present studies are part of an ongoing initiative to develop appropriate behavioral tasks for the evaluation of mouse models relevant to autism. We have previously reported profiles for sociability, preference for social novelty, and resistance to changes in a learned pattern of behavior, as well as other functional domains, for 10 inbred mouse strains of divergent genetic backgrounds. The present studies extend this multi-component behavioral characterization to several additional strains: C58/J, NOD/LtJ, NZB/B1NJ, PL/J, SJL/J, SWR/J, and the wild-derived PERA/EiJ. C58/J, NOD/LtJ, NZB/B1NJ, SJL/J, and PERA/EiJ demonstrated low sociability, measured by time spent in proximity to an unfamiliar conspecific, with 30-60% of mice from these strains showing social avoidance. In the Morris water maze, NZB/B1NJ had a persistent bias for the quadrant where the hidden platform was located during acquisition, even after 9 days of reversal training. A particularly interesting profile was found for C58/J, which had low social preference, poor performance in the T-maze, and overt motoric stereotypy. Overall, this set of tasks and observational methods provides a strategy for evaluating novel mouse models in behavioral domains relevant to the autism phenotype.
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PMID:Social approach and repetitive behavior in eleven inbred mouse strains. 1844 79

Malformations of cortical development (MCD) are one of the most common causes of neurological disabilities including autism and epilepsy. To disrupt cortical formation, methylazoxymethanol (MAM) or thalidomide (THAL) has been used to affect neurogenesis or vasculogenesis. Although previous models of MCD have been useful, these models primarily attack a single aspect of cortical development. We hypothesized that simultaneous prenatal exposure to MAM or THAL will lead to the development of a novel and specific type of brain maldevelopment. Rats were prenatally exposed to MAM and THAL. At early postnatal days, brains displayed abnormal ventricular size and hemispheric asymmetry due to altered brain water homeostasis. The postnatal brain was also characterized by gliosis in regions of focal leakage of the blood brain barrier. These morphological abnormalities gradually disappeared at adult stages. Although the adult MAM-THAL rats showed normal cortical morphology, abnormal hippocampal connectivity and mossy fiber sprouting persisted well into adulthood.
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PMID:Combined effects of prenatal inhibition of vasculogenesis and neurogenesis on rat brain development. 1893 Jan 44

Since World War II, approximately 80,000 new commercial synthetic chemicals have been released into the environment, with approximately 1500 new chemicals released annually. Most of these have not been adequately tested for their impacts on human health or their particular impacts on children and the developing fetus. Yet, children are exposed to hazardous chemicals through residues in their food, indoor and outdoor air pollution, and through household products and contaminated house dust. Many of these synthetic chemicals are persistent and bio-accumulative, remaining in the human body long after exposure. Developing fetuses acquire toxic chemicals that have bioaccumulated in the mother's body and readily cross the placental barrier. Babies are now born with many man-made chemicals in their small bodies. Newborns take in more through breast milk or formula. There are no tests to assess the combined impacts of the "chemical soup" to which children are exposed. WHO, UNICEF, and UNEP have reported a growing number of children's health impacts caused by exposure to hazardous chemicals, including asthma, birth defects, hypospadias, behavioral disorders, learning disabilities, autism, cancer, dysfunctional immune systems, neurological impairments, and reproductive disorders. WHO states that approximately 3 million children under the age of five die every year due to environmental hazards, and this is not limited to developing countries. All children, both in the developing and developed world are affected by exposure to hazardous chemicals. In 2004, the European Union's Ministerial Conference on Children's Environmental Health identified air pollution, unsafe water conditions, and lead exposure as the main culprits in the death and disabling of children in Europe. The conference found that by reducing exposure to hazardous chemicals, the lives of many children could be saved. The key issues in children's environmental health and potential policy and management remedies are examined from both national (Australian) and international perspectives.
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PMID:Children's environmental health: intergenerational equity in action--a civil society perspective. 1899 17

The effectiveness and safety of a group aquatic aerobic exercise program on cardiorespiratory endurance for children with disabilities was examined using an A-B study design. Sixteen children (11 males, five females) age range 6 to 11 years (mean age 9y 7mo [SD 1y 4mo]) participated in this twice-per-week program lasting 14 weeks. The children's diagnoses included autism spectrum disorder, myelomeningocele, cerebral palsy, or other developmental disability. More than half of the children ambulated independently without aids. Children swam laps and participated in relay races and games with a focus of maintaining a defined target heart rate zone. The strengthening component consisted of exercises using bar bells, aquatic noodles, and water resistance. The following outcomes were measured: half-mile walk/run, isometric muscle strength, timed floor to stand 3-meter test, and motor skills. Complaints of pain or injury were systematically collected. Significant improvements in the half-mile walk/run were observed, but not for secondary outcomes of strength or motor skills. The mean program attendance was 80%, and no injury was reported. Children with disabilities may improve their cardiorespiratory endurance after a group aquatic aerobic exercise program with a high adult:child ratio and specific goals to maintain training heart rates.
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PMID:Group aquatic aerobic exercise for children with disabilities. 1904 77

Emerging evidence supports the theory that some autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibility, specifically a reduced ability to excrete mercury (Hg), and exposure to Hg at critical developmental periods. Elemental/inorganic Hg is released into the air/water where it becomes methylated and accumulates in animal tissues. The US population is primarily exposed to methyl-Hg by fish consumption. In addition, many pharmaceuticals have been, and some continue to be, a ubiquitous source of danger because they contain mercurials. Mercurials may be found in drugs for the eye, ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions; in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides; in dental fillings and thermometers; and many other products. Hg has been found to cause immune, sensory, neurological, motor, and behavioural dysfunctions similar to traits defining/associated with ASDs, and that these similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Furthermore, a review of molecular mechanisms indicates that Hg exposure can induce death, disorganization and/or damage to selected neurons in the brain similar to that seen in recent ASD brain pathology studies, and this alteration may likely produce the symptoms by which ASDs are diagnosed. Finally, a review of treatments suggests that ASD patients who undergo protocols to reduce Hg and/or its effects show significant clinical improvements in some cases. In conclusion, the overwhelming preponderance of the evidence favours acceptance that Hg exposure is capable of causing some ASDs.
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PMID:A comprehensive review of mercury provoked autism. 1910 36

Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.
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PMID:Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. 1915 58


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