Glutamate, the main excitatory neurotransmitter in the vertebrate Central Nervous System, is involved in almost every aspect of brain physiology, and its signaling properties are severely affected in most neurodegenerative diseases. This neurotransmitter has to be efficiently removed from the synaptic cleft in order to prevent an over-stimulation of glutamate receptors that leads to neuronal death. Specific sodium-dependent membrane transporters, highly enriched in glial cells, elicit the clearance of glutamate. Once internalized, it is metabolized to glutamine by the glia-enriched enzyme Glutamine synthetase. Accumulated glutamine is released into the extracellular space for its uptake into pre-synaptic neurons and its conversion to glutamate that is packed into synaptic vesicles completing the glutamate/glutamine cycle. Diverse chemical compounds, like organophosphates, directly affect brain chemistry by altering levels of neurotransmitters in the synaptic cleft. Organophosphate compounds are widely used as pesticides, and all living organisms are continuously exposed to these substances, either in a direct or indirect manner. Its metabolites, like the diethyl dithiophosphate, are capable of causing brain damage through diverse mechanisms including perturbation of neuronal-glial cell interactions and have been associated with attention-deficit disorders and other mental illness. In order to characterize the neurotoxic mechanisms of diethyl dithiophosphate, we took advantage of the well characterized model of chick cerebellar Bergmann glia cultures. A significant impairment of [3H] d-Aspartate transport was found upon exposure to the metabolite. These results indicate that glia cells are targets of neurotoxic substances such as pesticides and that these cells might be critically involved in the associated neuronal death.

中文翻译：

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神经毒素二乙基二硫代磷酸酯会损害培养的Bergmann胶质细胞中的谷氨酸转运。

谷氨酸是脊椎动物中枢神经系统的主要兴奋性神经递质，几乎参与了大脑生理的各个方面，其信号传导特性在大多数神经退行性疾病中均受到严重影响。为了防止谷氨酸受体的过度刺激导致神经元死亡，必须从突触间隙中有效地去除这种神经递质。高度依赖神经胶质细胞的特定的钠依赖性膜转运蛋白引起谷氨酸的清除。一旦内在化，它就会通过富含神经胶质的酶谷氨酰胺合成酶代谢为谷氨酰胺。累积的谷氨酰胺被释放到细胞外空间，以摄取到突触前神经元中，并转化为谷氨酸，后者被填充到突触小泡中，从而完成了谷氨酸/谷氨酰胺循环。各种有机化合物（如有机磷酸酯）会通过改变突触间隙中神经递质的水平直接影响大脑的化学反应。有机磷酸酯化合物被广泛用作农药，所有活生物体都以直接或间接方式连续暴露于这些物质。它的代谢产物，如二乙基二硫代磷酸酯，能够通过多种机制引起脑损伤，包括扰动神经元-神经胶质细胞相互作用，并与注意力缺陷障碍和其他精神疾病有关。为了表征二乙基二硫代磷酸酯的神经毒性机制，我们利用了特征良好的小脑小脑Bergmann胶质细胞培养物模型。暴露于代谢产物后，发现[3H] d-天冬氨酸转运受到显着损害。