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

✍ Scribed by Harvey R. Weiss; Xia Liu; Qihang Zhang; Oak Z. Chi

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 155 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21378

✦ Synopsis

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 O~2~ consumption that might be associated with autism. We also examined whether the altered cerebral O~2~ 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 (^14^C‐iodoantipyrine) and O~2~ consumption (cryomicrospectrophotometry) were determined in isoflurane‐anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O~2~ consumption in the cortex (6.2 ± 0.6 ml O~2~/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 O~2~ 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 O~2~ consumption was reduced. This might have important implications in the treatment of autism. © 2007 Wiley‐Liss, Inc.