Reduced Number of Benzodiazepine Binding Sites and Decreased Density of GABAA Receptors in the Hippocampal Formation of Autistic Individuals
Session 1: Neuropathology of Autism
G.J. Blatt*, J.T. Guptill, A. Booker, C.M. Fitzgerald, T.L. Kemper and M.L. Bauman.
Dept. of Anatomy and Neurobiology, Boston Univ. Sch. Med., Boston MA 02118.
Initially, a survey of 8 neurotransmitter receptor types from 4 systems using in vitro ligand binding autoradiography was conducted in 4 autistic and 3 control brains aged 16-24 years with the finding of statistically significant differences only in the GABA receptor types. A two-way nested ANOVA followed with a posteriori between group comparisons test using the ad hoc Bonferroni test demonstrated in the autistic cases, a 15-35% decrease in the density of [3H]flunitrazepam labeled benzodiazepine (BZD) binding sites in stratum pyramidale of CA2, prosubiculum and subiculum and in stratum moleculare in the subiculum. Four additional hippocampal laminae demonstrated a trend for significance. The single concentration study was followed up with a 7 concentration saturation binding study generating curves to compare [3H]flunitrazepam binding to BZD sites in the mid-hippocampus of the same 4 autistic and 3 control males. Quantification of hippocampal lamina of autistic vs. control demonstrated a reduction in Bmax indicating a decreased number of benzodiazepine binding sites in the autistic group. In contrast, the KD values indicated that there was no difference in binding affinity between groups. We had also demonstrated from the initial survey that the density of [3H]muscimol labeled GABAA receptors were significantly reduced in stratum pyramidale of CA1, the highest binding region that also showed a trend for significance in the [3H]flunitrazepam binding. These data are the first to demonstrate in tissue sections an alteration in the GABAergic system in specific hippocampal laminae in autism. We are now analyzing saturation binding data from [3H]muscimol labeled GABAA receptors and conducting similar studies in the cerebellum. Supported by The Autism Research Foundation (TARF). Tissue for this study was obtained from the Harvard Brain Tissue Resource Center and the University of Miami and University of Maryland Brain Banks.
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