Purcell A E, Jeon O H, Zimmerman A W, Blue M E, Pevsner J
Department of Neurology, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Neurology. 2001 Nov 13;57(9):1618-28. doi: 10.1212/wnl.57.9.1618.
Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder.
To identify genes with abnormal expression levels in the cerebella of subjects with autism.
Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR with reverse transcription and Western blotting. alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex.
The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p < 0.05).
Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.
对自闭症患者大脑的研究已确定小脑和海马体等区域存在解剖学和病理学变化。然而，对于该疾病发病机制中涉及的分子却知之甚少。
鉴定自闭症患者小脑中表达水平异常的基因。
共收集了10名自闭症患者和23名匹配对照的脑样本，主要来自小脑。使用两种cDNA微阵列技术来鉴定在自闭症中显著上调或下调的基因。通过逆转录聚合酶链反应和蛋白质免疫印迹法研究了微阵列分析鉴定的几个基因的异常mRNA或蛋白质水平。使用受体放射自显影术检测了小脑、尾状核 - 壳核和前额叶皮质中的α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）和N - 甲基 - D - 天冬氨酸（NMDA）型谷氨酸受体密度。
自闭症中几个基因的mRNA水平显著升高，包括兴奋性氨基酸转运体1和谷氨酸受体AMPA 1，这两个都是谷氨酸系统的成员。进一步分析发现谷氨酸系统中其他几个分子的蛋白质或mRNA水平存在异常，包括谷氨酸受体结合蛋白。自闭症患者小脑中AMPA型谷氨酸受体密度降低（p < 0.05）。
自闭症患者小脑的AMPA型谷氨酸受体和谷氨酸转运体可能存在特定异常。这些异常可能直接参与该疾病的发病机制。
