Alterations in GABAergic biomarkers in the autism brain: Research findings and clinical implications

Gene J. Blatt, S. Hossein Fatemi

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Autism is a pervasive developmental disorder characterized by repetitive stereotyped behavior, social-emotional deficits, and delayed or absent language abilities. There are known neuropathologies in the autism brain affecting limbic, cerebellar, and cortical structures but the neurochemical profile of affected individuals, revealed in postmortem tissue studies, is only recently emerging. One major component that appears highly impacted in autism is the GABAergic system. It is now apparent that there are widespread significant effects in many distributed regions in the autism brain revealed by histochemical, autoradiographic, and biochemical studies. The key synthesizing enzymes for GABA, glutamic acid decarboxylase type 65 and 67 (GAD65 and GAD67), are decreased in the cerebellum and closer examination of mRNA levels revealed that it is largely due to decreases in Purkinje cells and a subpopulation of larger dentate neurons as measured by in situ hybridization studies. Other cell types had either normal GAD levels (Golgi cells, smaller dentate interneurons, and stellate cells) or increased levels (basket cells). GABA receptor density, number, and protein expression are all decreased in the cerebellum and in select cortical areas. GABA A and GABA B subunit protein expression was significantly reduced in cerebellum, BA 9 and BA 40. Benzodiazepine binding sites were significantly reduced in the hippocampus and anterior cingulate cortex (BA 24). Taken together, data from these studies suggest that there is a marked dysregulation of the inhibitory GABA system in the autism brain affecting particular biomarkers localized to specific cell types and lamina likely influencing circuitry and behavior.

Original languageEnglish (US)
Pages (from-to)1646-1652
Number of pages7
JournalAnatomical Record
Volume294
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Autism
  • BA 40
  • BA 9
  • Cerebellum
  • GABA

Fingerprint Dive into the research topics of 'Alterations in GABAergic biomarkers in the autism brain: Research findings and clinical implications'. Together they form a unique fingerprint.

  • Cite this