Alteration of Neural Development In the Brain of Adult BTBR T+ tf/J Mice, an Animal Model for Autism

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2012-12

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University of Hawaii at Manoa

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Autism is a growing spectrum of social impairment disorders resulting from neurological abnormalities and is characterized by symptoms of impaired social, communication skills and motor defects. It seems to result from distorted neural development. Under the supervision of Dr. Frederic Mercier, this research project aimed to characterize the potential alterations of connective tissue structures in the brain of the mutant BTBR T+ tf/J mouse, a model of autism. We have described anatomical alterations of the meninges, vasculature and fractones, the specialized extracellular matrix (ECM) of the subventricular zone, in the forebrain and midbrain of adult BTBR T+ tf/J mice by comparison with B6 control mice. We used Immunofluorescence histochemistry for laminin, a major ECM marker, on series of coronal sections of adult BTBR T+ tf/J and B6 brains. We used bisbenzidine cell nucleus staining and N-sulfated heparan sulfate proteoglycans (NS-HSPG) to further characterize series of brain sections containing the amygdala and hippocampus. The results showed significant defects in the connective tissue (meninges) and ECM throughout the series of sections examined. In the brain of BTBR T+ tf/J mice, the volume of lateral ventricles was significantly reduced, the falx cerebri (a meningeal projection that separated the brain into two hemispheres) was elongated, the arteries bloated and the choroid plexus atrophied. Moreover, fractone numbers in BTBR T+ tf/J mice were smaller in the SVZ of the anterior portion of the lateral ventricles than that of wild type mice.

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31 pages

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