Reduced GABAA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism

被引:125
|
作者
Oblak, Adrian L. [1 ]
Gibbs, Terrell T. [2 ]
Blatt, Gene J. [1 ]
机构
[1] Boston Univ, Sch Med, Dept Anat & Neurobiol, Lab Autism Neurosci Res, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA
基金
美国国家卫生研究院;
关键词
GABA; Autism; Neuropathology; PCC; FFG; MESSENGER-RNA LEVELS; FACE PERCEPTION; RHESUS-MONKEY; AUTOBIOGRAPHICAL MEMORY; HIPPOCAMPAL-FORMATION; SINGLE NEURONS; NEURAL SYSTEMS; CHILDREN; EPILEPSY; AREA;
D O I
10.1016/j.brainres.2010.09.021
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Individuals with autism display deficits in the social domain including the proper recognition of faces and interpretations of facial expressions. There is an extensive network of brain regions involved in face processing including the fusiform gyrus (FFG) and posterior cingulate cortex (PCC). Functional imaging studies have found that controls have increased activity in the PCC and FFG during face recognition tasks, and the FFG has differential responsiveness in autism when viewing faces. Multiple lines of evidence have suggested that the GABAergic system is disrupted in the brains of individuals with autism and it is likely that altered inhibition within the network influences the ability to perceive emotional expressions. On-the-slide ligand binding autoradiography was used to determine if there were alterations in GABA(A) and/or benzodiazepine binding sites in the brain in autism. Using H-3-muscimol and H-3-flunitrazepam we could determine whether the number (B-max), binding affinity (K-d), and/or distribution of GABA(A) receptors and benzodiazepine binding sites (BZD) differed from controls in the FFG and PCC. Significant reductions were found in the number of GABA(A) receptors and BZD binding sites in the superficial layers of the PCC and FFG, and in the number of BZD binding sites in the deep layers of the FFG. In addition, the autism group had a higher binding affinity in the superficial layers of the GABA(A) study. Taken together, these findings suggest that the disruption in inhibitory control in the cortex may contribute to the core disturbances of socio-emotional behaviors in autism. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:218 / 228
页数:11
相关论文
共 50 条
  • [21] Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABAA receptors
    Tan, Kelly R.
    Baur, Roland
    Charon, Sebastien
    Goeldner, Maurice
    Sigel, Erwin
    JOURNAL OF NEUROCHEMISTRY, 2009, 111 (05) : 1264 - 1273
  • [22] A Closer Look at the High Affinity Benzodiazepine Binding Site on GABAA Receptors
    Sigel, Erwin
    Luescher, Benjamin P.
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2011, 11 (02) : 241 - 246
  • [23] Blockade of adenosine A, receptors in the posterior cingulate cortex facilitates memory in rats
    Pereira, GS
    Souza, TME
    Vinadé, ERC
    Choi, H
    Rodrigues, C
    Battastini, AMO
    Izquierdo, I
    Sarkis, JJF
    Bonan, CD
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 437 (03) : 151 - 154
  • [24] ANATOMICAL EVIDENCE FOR MEDIAL PULVINAR CONNECTIONS WITH THE POSTERIOR CINGULATE CORTEX, THE RETROSPLENIAL AREA, AND THE POSTERIOR PARAHIPPOCAMPAL GYRUS IN MONKEYS
    BALEYDIER, C
    MAUGUIERE, F
    JOURNAL OF COMPARATIVE NEUROLOGY, 1985, 232 (02) : 219 - 228
  • [25] Prevalence between different α subunits performing the benzodiazepine binding sites in native heterologous GABAA receptors containing the α2 subunit
    del Río, JC
    Araujo, F
    Ramos, B
    Ruano, D
    Vitorica, J
    JOURNAL OF NEUROCHEMISTRY, 2001, 79 (01) : 183 - 191
  • [26] Change in allosteric coupling between the GABA and the benzodiazepine binding sites of GABAA receptors in the Planum temporale from schizophrenic subjects
    Pralong, D
    Tomaskovic-Crook, E
    Dean, B
    Copolov, D
    SCHIZOPHRENIA RESEARCH, 2000, 41 (01) : 249 - 249
  • [27] Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia
    Newell, Kelly A.
    Zavitsanou, Katerina
    Jew, Stephen Kum
    Huang, Xu-Feng
    PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2007, 31 (01): : 225 - 233
  • [28] Ionotropic glutamate receptor binding in the posterior cingulate cortex in schizophrenia patients
    Newell, KA
    Zavitsanou, K
    Huang, XF
    NEUROREPORT, 2005, 16 (12) : 1363 - 1367
  • [29] GABAA Receptor Benzodiazepine Binding Sites and Motor Impairments in Parkinson's Disease
    Bohnen, Nicolaas I.
    Barr, Jaimie
    Vangel, Robert
    Roytman, Stiven
    Paalanen, Rebecca
    Frey, Kirk A.
    Scott, Peter J. H.
    Kanel, Prabesh
    BRAIN SCIENCES, 2023, 13 (12)
  • [30] Emotional valence modulates activity in the posterior fusiform gyrus and inferior medial prefrontal cortex in social perception
    Geday, J
    Gjedde, A
    Boldsen, AS
    Kupers, R
    NEUROIMAGE, 2003, 18 (03) : 675 - 684