Abstract
Autism is a neurodevelopmental disorder that is often comorbid with seizures. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in brain. GABAB receptors play an important role in maintaining excitatory-inhibitory balance in brain and alterations may lead to seizures. We compared levels of GABAB receptor subunits GABAB receptor 1 (GABBR1) and GABAB receptor 2 (GABBR2) in cerebellum, Brodmann's area 9 (BA9), and BA40 of subjects with autism and matched controls. Levels of GABBR1 were significantly decreased in BA9, BA40, and cerebellum, while GABBR2 was significantly reduced in the cerebellum. The presence of seizure disorder did not have a significant impact on the observed reductions in GABAB receptor subunit expression. Decreases in GABAB receptor subunits may help explain the presence of seizures that are often comorbid with autism, as well as cognitive difficulties prevalent in autism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 64-69 |
| Number of pages | 6 |
| Journal | Cerebellum |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 2009 |
Bibliographical note
Funding Information:All experimental procedures were approved by the Institutional Review Board of the University of Minnesota School of Medicine. Postmortem blocks of parietal cortex (BA40), superior frontal cortex (BA9), and cerebellum (lobar origin unknown) were obtained from the Autism Research Foundation and several brain banks (the NICHD Brain and Tissue Bank for Developmental Disorders; TARF; the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH068855; the Brain Endowment Bank, which is funded in part by the National Parkinson Foundation, Inc., Miami, FL, USA; and the Autism Tissue Program). These samples, which have been used by our laboratory previously, are some of the most well-characterized and most-studied brain collections used by multiple groups (for review, [16]). All samples were stored at −80°C until use. Samples were derived from three groups of subjects (cerebellum: N=4–6 from subjects with autism, N=8–10 from control subjects; BA9: N=4–6 from subjects with autism, N=3 from control subjects; BA40: N=5–8 from subjects with autism, N=6 from control subjects). Consent from next of kin was given to the respective institutions. DSM-IV diagnoses were established prior to death by neurologists and psychiatrists using information from all available medical records and from family interviews. Details regarding the subject selection, diagnostic process, and tissue processing were collected by the Autism Research Foundation. Samples were matched for age, gender, and PMI. All demographic information is listed in Table 1. Seven out of nine subjects with autism had seizure disorder, and all subjects with autism displayed varying degrees of mental retardation (personal communication from Dr. Margaret Bauman). None of the controls had any known history of neuropsychiatric disorders, seizure disorder, or mental retardation.
Funding Information:
Acknowledgements Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders (University of Maryland); TARF; the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH068855; the Brain Endowment Bank, which is funded in part by the National Parkinson Foundation, Inc., Miami, FL, USA; and the Autism Tissue Program and is gratefully acknowledged. Grant support by National Institute of Child Health and Human Development (#5R01HD052074-01A2) to SHF is gratefully acknowledged.
Keywords
- Autism
- BA40
- BA9
- Cerebellum
- GABBR1
- GABBR2