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

Abstract

The 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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Tài liệu tham khảo

10.1016/j.tins.2007.06.002

10.1111/j.1749-6632.2001.tb03476.x

10.1111/j.1469-1809.2006.00253.x

10.1093/brain/121.5.889

Barker J.L., 1998, GABAergic cells and signals in CNS development, Perspectives on Developmental Neurobiology, 5, 305

10.1212/WNL.35.6.866

10.1523/JNEUROSCI.3340-04.2004

10.1016/0091-3057(87)90006-2

10.1152/physrev.00017.2006

10.1523/JNEUROSCI.12-03-00924.1992

10.1023/A:1013238809666

10.1016/j.nurt.2009.01.019

10.1002/cne.902790202

10.1016/S1364-6613(00)01483-2

10.1111/j.1460-9568.2007.05825.x

10.1001/archpsyc.64.7.793

10.1523/JNEUROSCI.5169-06.2007

10.1212/WNL.58.3.428

10.1177/1073858403253552

10.1016/j.cnr.2006.06.003

10.1016/j.brainresrev.2004.03.003

10.1038/nn1258

10.1007/s002130050148

10.1093/brain/118.1.279

10.1111/j.1399-0004.2007.00822.x

10.1016/S0006-3223(02)01430-0

10.1007/s12311-008-0075-3

10.1007/s10803-008-0646-7

10.1016/S0306-4522(97)00244-3

10.1111/j.1528-1167.2005.01001.x

10.1111/j.1469-8749.1987.tb08506.x

10.1177/1362361301005003005

10.1177/1744629507083585

10.1007/s10803-006-0226-7

10.1001/archpsyc.65.10.1166

10.1176/ajp.154.8.1047

10.1176/appi.ajp.157.12.1994

10.1093/cercor/bhj135

10.1016/j.neubiorev.2005.06.006

10.1515/REVNEURO.2004.15.4.279

10.1177/7010.2006.00237

10.1002/cne.901950309

10.1073/pnas.0502624102

10.1093/brain/awl164

10.1016/j.biopsych.2006.08.004

10.1073/pnas.0600674103

10.1007/s10803-008-0555-9

10.1162/089892998562924

10.1111/j.1600-0404.2009.01234.x

10.1016/j.neuropharm.2006.03.003

10.1523/JNEUROSCI.20-14-05401.2000

10.1093/brain/awl287

10.1126/science.290.5489.131

10.1086/433195

Marrosu F., 1987, Paradoxical reactions elicited by diazepam in children with classic autism, Functional Neurology, 2, 355

10.1007/s004150170136

10.1073/pnas.0508591102

Mohler H., 1995, GABAA‐receptor subtypes in vivo: cellular localization, pharmacology and regulation, Advances in Biochemical Psychopharmacology, 48, 41

10.1007/BF01694546

10.1016/j.bcp.2004.07.025

10.1111/j.1460-9568.2006.04775.x

10.3758/CABN.3.1.17

10.1016/j.neuroscience.2005.04.013

10.1001/archneur.1988.00520300086024

10.1089/cap.2006.17303

10.1007/BF00237497

10.1001/archneurpsyc.1937.02260220069003

10.1523/JNEUROSCI.2877-04.2004

10.1523/JNEUROSCI.2419-07.2007

10.1002/cne.901980111

Posner M.I., 1999, Development of brain networks for orienting to novelty, Zhurnal Vyssheĭ Nervnoĭ Deiatelnosli Imeni I P Pavlova, 49, 715

10.3758/CABN.7.4.391

Rainnie D.G., 1992, Kindling‐induced long‐lasting changes in synaptic transmission in the basolateral amygdala, Journal of Neurophysiology, 67, 443, 10.1152/jn.1992.67.2.443

10.1073/pnas.0501434102

10.1002/cne.901950308

10.1002/(SICI)1096-9861(19960930)373:4<529::AID-CNE5>3.0.CO;2-3

10.1176/ajp.153.11.1444

10.1034/j.1601-183X.2003.00037.x

Rutter M., 1970, Autism: concepts and consequences, Special Education, 59, 20

10.1016/S0140-6736(88)92468-3

10.1192/bjp.bp.107.036921

10.1002/(SICI)1096-8628(19980401)76:4<327::AID-AJMG8>3.0.CO;2-M

10.1523/JNEUROSCI.1285-06.2006

10.1016/j.biopsych.2007.06.028

10.1176/ajp.2006.163.8.1440

10.1007/s00401-009-0568-2

Speth R.C., 1980, The benzodiazepine receptor of mammalian brain, Federation Proceedings, 39, 3032

10.1007/s10802-007-9165-9

10.1016/S0306-4530(96)00035-2

10.1093/brain/awn099

10.1093/cercor/12.9.936

10.1089/cap.2005.15.452

10.1002/cne.902620208

10.1093/cercor/2.6.435-a

10.1002/cne.903590310

10.1097/00004583-199001000-00020

10.1016/j.neuroimage.2005.07.022

10.1016/0014-2999(89)90020-4

10.1001/archneur.1961.00450160014002

10.1007/s00401-006-0176-3

10.1002/jnr.21520

10.1002/aur.62

10.1002/jnr.21003

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Autism Research

Tập 2 Số 4

205-219

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