NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder.
NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder.
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DOI：
10.1186/s13229-015-0023-2
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发表时间：
2015
期刊：
影响因子：
6.2
通讯作者：
Ordway GA
中科院分区：
文献类型：
--
作者：
Chandley MJ;Crawford JD;Szebeni A;Szebeni K;Ordway GA
前扣带皮层（ACC）是一个参与调节与社会互动相关的行为的大脑区域，其破坏是自闭症谱系障碍（ASD）的核心特征。功能性脑成像研究表明，与正常发展的对照患者相比，ASD患者的ACC异常。然而，对于ASD中这些功能缺陷的细胞基础知之甚少。ACC中的锥体神经元是兴奋性谷氨酸能神经元，是ACC神经输出的关键细胞介质。本研究旨在探讨ACC锥体神经元在ASD脑病理中的潜在作用。来自精心匹配的ASD和典型发育对照供体的死后ACC组织从两个国家大脑收藏中获得。采用激光捕获显微解剖方法分别采集ACC第三层锥体神经元和周围星形胶质细胞。对分离的RNA进行反转录和终点PCR，检测与谷氨酸能神经传递相关的16个突触基因的表达水平。还从前额皮质（Brodmann区10）收集细胞，以检查ACC中表现出与正常发育和ASD供者相比表达差异的基因。与正常发育的供体相比，ASD供体锥体神经元中NTRK2的表达水平明显降低。在ASD供体的锥体神经元中，GRIN1、GRM8、SLC1A1和GRIP1的表达水平略有降低，但经过多次比较校正后，这些基因的表达水平没有统计学意义。激光捕获的相同脑皮层星形胶质细胞中，没有发现任何基因的表达差异。此外，从前额皮质激光捕获的锥体神经元中，NTRK2和其他突触基因的表达水平正常。这些研究证明了ASD中ACC新皮质锥体神经元的独特病理。NTRK2编码原肌球蛋白受体激酶B (TrkB)，神经营养因子通过其介导分化、可塑性和突触传递。因此，ACC中锥体神经元NTRK2表达的减少可能导致神经元活动异常，并破坏由该大脑区域介导的社会行为。本文的在线版本（doi:10.1186/s13229-015-0023-2）包含补充材料，仅供授权用户使用。
The anterior cingulate cortex (ACC) is a brain area involved in modulating behavior associated with social interaction, disruption of which is a core feature of autism spectrum disorder (ASD). Functional brain imaging studies demonstrate abnormalities of the ACC in ASD as compared to typically developing control patients. However, little is known regarding the cellular basis of these functional deficits in ASD. Pyramidal neurons in the ACC are excitatory glutamatergic neurons and key cellular mediators of the neural output of the ACC. This study was designed to investigate the potential role of ACC pyramidal neurons in ASD brain pathology. Postmortem ACC tissue from carefully matched ASD and typically developing control donors was obtained from two national brain collections. Pyramidal neurons and surrounding astrocytes were separately collected from layer III of the ACC by laser capture microdissection. Isolated RNA was subjected to reverse transcription and endpoint PCR to determine gene expression levels for 16 synaptic genes relevant to glutamatergic neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann area 10) to examine those genes demonstrating differences in expression in the ACC comparing typically developing and ASD donors. The level of NTRK2 expression was robustly and significantly lower in pyramidal neurons from ASD donors as compared to typically developing donors. Levels of expression of GRIN1, GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors, but statistical significance for these latter genes did not survive correction for multiple comparisons. No significant expression differences of any genes were found in astrocytes laser captured from the same neocortical area. In addition, expression levels of NTRK2 and other synaptic genes were normal in pyramidal neurons laser captured from the prefrontal cortex. These studies demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through which neurotrophic factors modify differentiation, plasticity, and synaptic transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby contribute to abnormal neuronal activity and disrupt social behavior mediated by this brain region. The online version of this article (doi:10.1186/s13229-015-0023-2) contains supplementary material, which is available to authorized users.
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影响因子：
1.9
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