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Available from: Robert T Schultz, Sep 27, 2015
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    • "For much of the history of postmortem studies of ASD pathology, brain abnormalities have been viewed as static [102], but the regression observed in 15–62% of autism cases has been linked to neurodegeneration and neuronal loss [103]. However, morphological markers of neurodegeneration have been reported only sporadically, including cytoplasmic homogenous inclusions in Purkinje cells in affected child [98], Purkinje and granule cells’ mineralization [87], and neurofibrillary degeneration in a 24-year-old autistic female with self-injurious behavior including head-banging [104]. "
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    ABSTRACT: IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.Conclusions The observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.
    09/2014; 2(1):141. DOI:10.1186/s40478-014-0141-7
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    • "Interestingly, cognitive rigidity, anxiety, and neophobia are cardinal features of autism spectrum disorder (ASD) [63], and accumulating evidence suggests that decreased neuronal area and neuronal hyperdensity are present in the limbic structures of affected individuals [64]. Further study of PTN KO mice might therefore have implications for the development of animal models of ASD. "
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    ABSTRACT: Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features.
    PLoS ONE 07/2014; 9(7):e100597. DOI:10.1371/journal.pone.0100597 · 3.23 Impact Factor
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    • "Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder (Mulvihill et al., 2009), which is characterized by impaired social interactions and enhanced repetitive or stereotyped behavior, as well as marked inflexibility to environmental contingency changes (American Psychiatric Association, 1994; Arndt et al., 2005; DiCicco-Bloom et al., 2006). The prevalence of autism is about 3–6 per 1000 people (Rutter, 2005). "
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    ABSTRACT: Neonatal isolation is a widely accepted model to study the long-term behavioral changes produced by the early life events. However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1-9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42-56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development.
    Frontiers in Behavioral Neuroscience 06/2014; 8:234. DOI:10.3389/fnbeh.2014.00234 · 3.27 Impact Factor
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