International Meeting for Autism Research: Altered Cyctoarchitecture, Decreased GABA and Serotonin Receptor Subtypes, but Normal Density of Neurons and Interneurons in the Posterior Cingulate Cortex and Fusiform Gyrus in Autism

Altered Cyctoarchitecture, Decreased GABA and Serotonin Receptor Subtypes, but Normal Density of Neurons and Interneurons in the Posterior Cingulate Cortex and Fusiform Gyrus in Autism

Saturday, May 22, 2010: 9:45 AM
Grand Ballroom AB Level 5 (Philadelphia Marriott Downtown)
9:45 AM
A. Oblak , Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA
T. Gibbs , Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA
T. Kemper , Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA
M. L. Bauman , Lurie Center/LADDERS; Anatomy and Neurobiology, MassGeneral Hosptial for Children/Harvard Medical School; Boston University School of Medicine, Lexington, MA
G. Blatt , Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA
Background: Striking characteristics of individuals with autism is a pervasive impairment in social interaction with others and difficulties in identifying facial expressions and emotions.  Processing the human face is at the focal point of most social interactions.  Atypical social behaviors have been observed in early development of children with autism and have led to the contention that autism is a condition where the processing of social information, particularly faces and emotions, is impaired.  Two areas involved in emotion and memory processing and face processing are the posterior cingulate cortex (PCC) and fusiform gyrus (FFG). 

Objectives: To determine whether there are alterations in cytoarchitecture, neuron and interneuron density, and GABA and serotonin receptor subtypes in the PCC and FFG in adult post-mortem autism and control brains.

Methods: Thionin stained sections were used to analyze the cytoarchitecture of the PCC and FFG and immunohistochemistry to identify parvalbumin and calbindin positive GABAergic interneurons.  Unbiased, design-based stereological principles were implemented to quantitatively assess the density of thionin, parvalbumin, and calbindin neurons.  Receptor binding autoradiography was used to determine the density of GABAergic (GABAA, GABAB, benzodiazepine) and serotonergic (5HT1A, 5HT2A) receptors and transporters (uptake sites; 5HTU). 

Results: Cytoarchitectonic abnormalities were observed in the PCC but not in the FFG in the autism cases.  The PCC had a poorly defined layer IV, displaced layer V neurons, and increased neurons in the white matter. There was no significant difference in the density of thionin-positive neurons or calbindin- and parvalbumin-positive interneurons in either region. Significant reductions in the density of GABAA and GABAB receptors, benzodiazepine binding sites, 5HT1A and 5HT2A receptors, and 5HTU were observed throughout the PCC and FFG.

Conclusions: The presence of cytoarchitectonic abnormalities in the PCC provides further support for the occurrence of developmental abnormalities within the limbic lobe in the brain in autism.  The reduced density of GABAergic and serotonergic receptors does not appear to be the result of a reduced density of neurons within the PCC or FFG, but could be the result of reduced receptors on dendrites or cell bodies or alterations in genes encoding GABA and serotonin receptors.  These receptor changes could result in altered synaptic transmission contributing to altered intrinsic and/or extrinsic circuitry with resultant altered processing of emotions and faces, and abnormal social behaviors.

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