Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
Toxicology. 2020 Jul;440:152500. doi: 10.1016/j.tox.2020.152500. Epub 2020 May 16.
Autism spectrum disorders (ASD) include neurodevelopmental disorders in which behavioral deficits can result from neuronal imbalance of excitation to inhibition (E/I) in the brain. Here we used RT-qPCR to screen for the expression of 99 genes associated with excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission in the cerebral cortex, hippocampus and cerebellum of rats in an established VPA model of ASD. The largest changes in the expression of glutamatergic genes were found in the cerebral cortex, where 12 genes including these encoding some of the subunits of the ionotropic glutamate receptors, were upregulated, while 2 genes were downregulated. The expression of genes encoding the presynaptic glutamatergic proteins vGluT1 and mGluR7 and PKA, involved in downstream glutamatergic signaling, was elevated more than 100-fold. Changes in GABAergic gene expression were found in the cortex, cerebellum and hippocampus; 3 genes were upregulated, and 3 were downregulated. In conclusion, these results revealed that, in the ASD model, several glutamatergic genes in the rat cerebral cortex were upregulated, which contrasts with small and balanced changes in the expression of GABAergic genes. The VPA rat model, useful in studying the molecular basis of ASD, may be suitable for testing experimental therapies in these disabilities.
自闭症谱系障碍（ASD）包括神经发育障碍，其行为缺陷可源于大脑中兴奋（谷氨酸能）与抑制（GABA 能）之间的神经元失衡。在这里，我们使用 RT-qPCR 筛选了与兴奋性（谷氨酸能）和抑制性（GABA 能）神经递质传递相关的 99 个基因在 ASD 的 VPA 模型大鼠大脑皮层、海马体和小脑中的表达。谷氨酸能基因表达的最大变化发生在大脑皮层，其中包括一些离子型谷氨酸受体亚基编码的 12 个基因上调，而 2 个基因下调。编码突触前谷氨酸蛋白 vGluT1 和 mGluR7 以及参与下游谷氨酸信号转导的 PKA 的基因表达升高了 100 多倍。在皮层、小脑和海马体中发现了 GABA 能基因表达的变化；3 个基因上调，3 个基因下调。总之，这些结果表明，在 ASD 模型中，大鼠大脑皮层中的几个谷氨酸能基因上调，这与 GABA 能基因表达的微小而平衡的变化形成对比。VPA 大鼠模型在研究 ASD 的分子基础方面很有用，可能适合在这些疾病中测试实验性治疗。
