Developmental alterations of raphe nuclei in autistic subjects 5-15 years of age- methods and technical limitations
Item
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Title
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Developmental alterations of raphe nuclei in autistic subjects 5-15 years of age- methods and technical limitations
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Identifier
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d_2009_2013:21cc5dd78fbb:11705
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identifier
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12280
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Creator
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Wegiel, Jarek,
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Contributor
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Probal Banerjee
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Date
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2013
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Language
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English
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Publisher
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City University of New York.
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Subject
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Neurosciences | Clinical psychology | Developmental psychology
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Abstract
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The role of the serotonergic system in autism is supported by more than 500 reports. They reveal a link between serotonergic system alterations and social deficits, repetitive behavior, hyperactivity, anxiety and obsessive compulsive behavior observed in autism. However, in spite of evidence of altered development of brain serotonergic system and contribution of these alterations to the autism phenotype, the raphe nuclei, which are the source of brain serotonin, have not been examined.;The aim of this stereological and quantitative immunofluorescence- based study of raphe nuclei in autistic subjects 5 to 15 years of age and age matched control subjects was to (a) establish methods of preparation, staining, and analysis of fixed human brainstem samples obtained from brain banks, and (b) characterize the pattern of developmental abnormalities which may contribute to the autistic phenotype.;Routine neuropathological brainstem dissection results in partial or complete loss of raphe nuclei integrity. From 9 autistic and 6 control subjects only four pairs 5 to 15 years of age were qualified for the study of raphe nuclei. Formalin-fixed brainstem was dehydrated and embedded in polyethylene glycol and cut into serial 50-um-thick sections. They were stained to estimate cell volume, and immunostained and examined by fluorescence microscopy to estimate the amount of tryptophan hydroxylase (TPH) which is a measure of serotonin synthesis level.;3-D reconstruction demonstrated topography and size of raphe nuclei and explained why preservation of raphe nuclei located in the midline required modification of brainstem sampling. Nucleator applied to TPH (+) sections revealed 24% smaller neuronal soma volume in the dorsal raphe nuclei of autistic subjects than in control group. Application of immunofluorescence and ImageJ software (NIH) revealed significant increase in tryptophan hydroxylase (TPH) immunofluorescence in spite of smaller size of raphe neurons.;These data indicate developmental impairment of neuron growth comparable to that observed in cortex and in subcortical structures. Enhanced TPH immunofluorescence in raphe neurons was consistent with enhanced immunoreactivity in serotonergic fibers in several brain regions of autistic subjects (Azmitia et al. 2011). Pathology detected in raphe neurons suggests that target brain areas were exposed to altered levels of serotonin, which may modify function of cerebral cortex and subcortical structures and contribute to the autistic phenotype.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
