Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism

Autism Research - Tập 2 Số 4 - Trang 205-219 - 2009
Adrian L. Oblak1, Terrell T. Gibbs2, Gene J. Blatt1
1Boston University School of Medicine, Anatomy and Neurobiology, Boston, Massachusetts
2Boston University School of Medicine, Pharmacology and Experimental Therapeutics, Boston, Massachusetts

Tóm tắt

AbstractThe anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio‐emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and gamma‐amino‐butyric acid (GABA) system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple‐concentration ligand‐binding study utilized 3H‐muscimol and 3H‐flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4%) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio‐emotional behaviors in autism.

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Autism Research

Tập 2 Số 4

205-219

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