Fatemi S Hossein, Halt Amy R, Stary Joel M, Kanodia Reena, Schulz S Charles, Realmuto George R
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware Street SE, Mayo Building, Box 392, Minneapolis, MN 55455, USA.
Biol Psychiatry. 2002 Oct 15;52(8):805-10. doi: 10.1016/s0006-3223(02)01430-0.
A limited number of reports have demonstrated abnormalities involving the glutamate and gamma amino butyric acid systems in blood and platelets of subjects with autism. To further investigate these studies, brain levels of rate limiting enzyme, glutamic acid decarboxylase, which is responsible for normal conversion of glutamate to gamma amino butyric acid in the brain, were investigated.
Postmortem cerebellar and parietal cortices of age (mean +/- SD for controls 23 +/- 4.2, autistic 25.2 +/- 5.2 cerebellum; controls 23.5 +/- 4.8, autistic 21.6 +/- 3.8 parietal cortex), gender and postmortem interval-matched autistic and control subjects (n = 8 control, n = 5 autism, cerebellum; n = 4 control, n = 5 autism, parietal cortex) were subjected to SDS-PAGE and western blotting. Brain levels of glutamic acid decarboxylase proteins of 65 and 67 kDa and beta-actin were determined.
Glutamic acid decarboxylase protein of 65 kDa was reduced by 48% and 50% in parietal and cerebellar (p <.02) areas of autistic brains versus controls respectively. By the same token, glutamic acid decarboxylase protein of 67 kDa was reduced by 61% and 51% in parietal (p <.03) and cerebellar areas of autistic brains versus controls respectively. Brain levels of beta-actin were essentially similar in both groups.
The observed reductions in glutamic acid decarboxylase 65 and 67 kDa levels may account for reported increases of glutamate in blood and platelets of autistic subjects. Glutamic acid decarboxylase deficiency may be due to or associated with abnormalities in levels of glutamate/gamma amino butyric acid, or transporter/receptor density in autistic brain.
少数报告显示，自闭症患者的血液和血小板中涉及谷氨酸和γ-氨基丁酸系统的异常。为了进一步研究这些情况，对大脑中负责将谷氨酸正常转化为γ-氨基丁酸的限速酶谷氨酸脱羧酶的水平进行了研究。
对年龄（对照组平均±标准差为23±4.2，自闭症患者小脑为25.2±5.2；对照组为23.5±4.8，自闭症患者顶叶皮质为21.6±3.8）、性别和死后间隔时间匹配的自闭症患者和对照组受试者（小脑：对照组8例，自闭症患者5例；顶叶皮质：对照组4例，自闭症患者5例）的小脑和顶叶皮质进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和蛋白质免疫印迹法检测。测定大脑中65 kDa和67 kDa的谷氨酸脱羧酶蛋白以及β-肌动蛋白的水平。
与对照组相比，自闭症患者大脑顶叶和小脑区域中65 kDa的谷氨酸脱羧酶蛋白分别减少了48%和50%（p<0.02）。同样，与对照组相比，自闭症患者大脑顶叶和小脑区域中67 kDa的谷氨酸脱羧酶蛋白分别减少了61%和51%（p<0.03）。两组的大脑β-肌动蛋白水平基本相似。
观察到的65 kDa和67 kDa谷氨酸脱羧酶水平降低可能解释了自闭症患者血液和血小板中谷氨酸含量升高的报道。谷氨酸脱羧酶缺乏可能是由于自闭症大脑中谷氨酸/γ-氨基丁酸水平异常，或转运体/受体密度异常所致，或与之相关。
