Skip to main content
Article thumbnail
Location of Repository

Autism counts. Stereological studies on human postmortem brains and a mouse model for autism

By I.A.J. van Kooten

Abstract

Autism is a neurodevelopmental disorder with a strong genetic component and several known environmental risk factors. Classical neuropathology studies have reported consistent findings in the limbic system, cerebellum and cerebral cortex of patients with autism. However, the neurobiological mechanism underlying these gross morphological alterations remain to be established and it is not known whether these alterations reflect different aspects of a unique neuropathologic defect or represent different morphological phenotypes of the disorder. In addition, it has not been possible to find functional interpretations of the gross morphological alterations reported in patients with autism. Furthermore, all studies had to contend with small sample sizes, biased quantification techniques and high percentages of patients suffering form comorbid mental retardation and epilepsy. In the present thesis we investigated cytoarchitectonic abnormalities in specific regions within the cerebral cortex related to social functioning in both postmortem brains from patients with autism and an animal model for autism, using high precision design-based stereology. To overcome the aforementioned difficulties in autism research we generated a unique case series, consisting of 7 brains of patients with autism compared to 10 matched controls, developed in the framework of the Autism Brain Atlas Project supported by the U.S. Autism Tissue Program and Autism Speaks (New York, NY, USA). Showing the validity of the sample, we corroborated previous findings of minicolumnar abnormalities in an independent sample. Furthermore, a potential neurobiological correlate of alterations in the fusiform gyrus (FG) as described in clinical and imaging studies was found. Besides this, some patients with autism showed altered morphology of the Von Economo neurons (VENs) within the anterior cingulate cortex (ACC) and frontoinsular cortex (FI) (VENs play an important role in the coordination of distributed neuronal activity involving social functioning). Moreover, our analyses revealed that the maternal influenza infection mouse model cannot be applied to understand the underlying mechanisms of postnatal brain overgrowth in autism, and exposure of pregnant mice to human influenza virus at E9.5 does not reproduce the entire neuropathology of autism with respect to the amygdala. Although studies on autism neuropathology are revealing, further research is necessary to clarify the influence of neuropathological alterations in the etiology of autism. The results of the present study argue for a neural systems approach in autism research, rather then investigating individual brains regions. Thus, the present study may be seen as starting point to open new horizons in autism research. In order to get more insight into the functional interpretation of neuropathological findings, future studies should focus on the brain regions involved in the neuronal networks mediating face processing as well as on the projection areas and function of the VENs, using quantitative histology. In addition, detailed analyses on appropriate animal models (combining transgenic approaches with environmental hits during development) might explain the potential developmental origin of the described neuropathological alterations in autism

Publisher: Utrecht University
Year: 2008
OAI identifier: oai:dspace.library.uu.nl:1874/31079
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dspace.library.uu.nl:80... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.