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Increased cerebral oxygen consumption in Eker rats and effects of N‐methyl‐D‐aspartate blockade: Implications for autism
Author(s) -
Weiss Harvey R.,
Liu Xia,
Zhang Qihang,
Chi Oak Z.
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21378
Subject(s) - nmda receptor , cerebral blood flow , endocrinology , medicine , hippocampus , cerebral cortex , chemistry , receptor , anesthesia
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.