Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism

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

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Because there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that these animals would have an altered regional cerebral O2 consumption that might be associated with autism. We also examined whether the altered cerebral O2 consumption was related to changes in the importance of N-methyl-D-aspartate (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg, competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane- anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O2 consumption in the cortex (6.2 ± 0.6 ml O2/min/100 g Eker vs. 4.7 ± 0.4 Long Evans), hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated in Eker rats at baseline, but cerebral O 2 extraction was similar. CGS-19755 significantly lowered O 2 consumption in the cortex (2.8 ± 0.3), hippocampus, and pons of the Long Evans rats but had no effect on cortex (5.8 ± 0.8) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. NMDA receptor protein levels (NR1 subunit) were similar between groups. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not related to NMDA receptor activation. In fact, the importance of NMDA receptors in the control of basal cerebral O2 consumption was reduced. This might have important implications in the treatment of autism.

Original languageEnglish (US)
Pages (from-to)2512-2517
Number of pages6
JournalJournal of Neuroscience Research
Volume85
Issue number11
DOIs
StatePublished - Aug 15 2007

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Keywords

  • Autism spectrum disorder
  • Cerebral O consumption
  • Cerebral blood flow
  • Excitatory amino acids
  • Rats

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