科学家发现癫痫，自闭症和精分的根源
科学家发现癫痫，自闭症和精分的根源（英文）2008-12-11 11:44Scientists find potential clues to epilepsy, autism, schizophrenia
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Washington, Dec 10 (ANI): Rice University researchers claim to have uncovered a potential clue to the roots of neurological disorders like epilepsy, autism and schizophrenia.
The research team led by Eric Howlett discovered an unanticipated connection between glutamate an amino acid and neurotransmitter in much of the food we eat and phosphoinositide 3-kinase (PI3K), an enzyme that, Howlett found, regulates the activity of neurons.
In the study conducted using a fruit fly, they found that negative feedback mediated by PI3K regulates the excitability of neurons, an issue in a number of ailments that include neurofibromatosis.
A mutation in a glutamate receptor gene common to both the fruit fly and humans has the ability to disrupt that regulatory mechanism.
Howlett found the fruit fly’s metabotropic glutamate receptor (DmGluRA) gene, when mutated, increased the excitability of the neuron by preventing PI3K from doing its job.
What we found was that glutamate, which is released due to neuronal activity, feeds back onto metabotropic glutamate receptors on the same neurons that released it in the first place, he said.
This leads to the activation of PI3K and ultimately to the dampening of the amount of glutamate that is released. Without that regulation, he said, things inside the cell can go terribly wrong, he added.
Michael Stern, co-researcher and a professor of biochemistry and cell biology, said that discovering the negative feedback loop that keeps neurons stable was key, however further studies are required.
We know that glutamate activates mGluR and PI3K, but we don’t know how, he said.
There are almost certainly a number of intermediates that remain to be identified, and we have several candidates we’re looking into, he added.
The study is published online by the Public Library of Science Genetics. (ANI)
12月10日华盛顿ANI报道：赖斯大学的研究人员声称已发现了癫痫，自闭症和精神分裂症等神经障碍的潜在根源。
由埃里克?赫尔特率领的研究小组发现在多种食物中谷氨酸和神经递质之间有意外的连接，并发现一种可以调节神经元活性的酶——磷脂酰肌醇-3-激酶(PI3K)。在用果蝇为对象的实验中，研究人员发现由PI3K介导的负反馈可以调节神经的兴奋性，这个问题存在于神经纤维瘤等许多疾病。共同存在于果蝇和人类的谷氨酸受体基因的突变可以破坏这种调节机制。赫尔特发现当果蝇的亲代谢性谷氨酸盐受体基因发生突变时，将通过阻止PI3K的作用来增加神经元的兴奋性。他说我们发现神经兴奋时释放的谷氨酸反馈作用于早先释放谷氨酸同一个神经元的亲代谢性谷氨酸盐受体。这就激活了PI3K并且完全抑制所要释放的谷氨酸的数量.没有这一调节,细胞内的物质将出现可怕的差错.
生化和细胞生物学教授、合作研究者迈克尔?斯坦说关键是发现保持神经元保持稳定的负反馈环路,所以尚需进一步研究。他说到我们知道谷氨酸激活亲代谢性谷氨酸盐受体和PI3K，但并不知道机理，可以肯定的是任然有许多的中间介质等待我们去发现，目前我们已经着手其中几种了。
该研究发表于网上:遗传科学的公共图书馆。
