Cerebral O(2) consumption in young Eker rats, effects of GABA blockade: implications for autism.
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 O(2) consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O(2) 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 (70-100g) were divided into control and bicuculline (1mg/kg/min for 2 min then 0.1mg/kg/min for 13 min, GABA(A) receptor antagonist) treated animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O(2) consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O(2) consumption in the cortex (6.3+/-0.7 ml O(2)/min/100g Eker vs. 5.1+/-0.2 ml O(2)/min/100g 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 O(2) extractions were similar. Bicuculline significantly increased O(2) 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 O(2) consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABA(A) receptor in the brains of Eker rats. This may have important implications in the treatment of autism.
Weiss
Harvey R
HR
Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854-5635, USA. hweiss@umdnj.edu
Liu
Xia
X
Chi
Oak Z
OZ
D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology* / Q000627:therapeutic use; D002531:Cerebellum / Q000098:blood supply / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D011149:Pons / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000187:drug effects; D014402:Tuberous Sclerosis / Q000188:drug therapy / Q000378:metabolism
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D001640:Bicuculline