Cerebral O2 consumption in young Eker rats, effects of GABA blockade: implications for autism

Harvey R. Weiss, Xia Liu, Oak Z. Chi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Since there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that the increased regional cerebral O2 consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O2 consumption was related to changes in the activity of the gamma-aminobutyric acid (GABA) inhibitory system. Young (4 weeks) male control Long Evans (n = 14) and Eker (n = 14) rats (70-100 g) were divided into control and bicuculline (1 mg/kg/min for 2 min then 0.1 mg/kg/min for 13 min, GABAA receptor antagonist) treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O2 consumption in the cortex (6.3 ± 0.7 ml O2/min/100 g Eker vs. 5.1 ± 0.2 ml O2/min/100 g control), hippocampus and cerebellum, but not the pons. Regional cerebral blood flow was also elevated in the cortex and hippocampus in Eker rats at baseline, but cerebral O2 extractions were similar. Bicuculline significantly increased O2 consumption in the cortex (6.5 ± 0.3) and all other regions of the control rats, but had no effect on cortex (5.9 ± 1.5) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABAA receptor in the brains of Eker rats. This may have important implications in the treatment of autism.

Original languageEnglish (US)
Pages (from-to)517-521
Number of pages5
JournalInternational Journal of Developmental Neuroscience
Volume26
Issue number5
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Developmental Neuroscience
  • Developmental Biology

Keywords

  • Autism spectrum disorder
  • Cerebral O consumption
  • Cerebral blood flow
  • GABA receptors
  • Gamma-aminobutyric acid

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