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Differentiation renders susceptibility to excitotoxicity in HT22 neurons

Neural Regeneration Research 2013年第14期8卷 1297-1306页

作者： Minchao He Jun Liu haowu Cheng Yigang Xing William Z Suo Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen University Laboratory for Alzheimer's Disease & Aging Research Veterans Affairs Medical Center Department of Neurology University of Kansas Medical Center Molecular & Integrative Physiology University of Kansas Medical Center

HT22 is an immortalized mouse hippocampal neuronal cell line that does not express cholinergic and glutamate receptors like mature hippocampal neurons in vivo. This in part prevents its use as a model for mature hippocampal neurons in memory-related studies. We now report that HT22 cells were appropriately induced to differentiate and possess properties similar to those of mature hippocampal neurons in vivo, such as becoming more glutamate-receptive and excitatory. Results showed that sensitivity of HT22 cells to glutamate-induced toxicity changed dramatically when comparing undifferentiated with differentiated cells, with the half-effective concentration for differentiated cells reducing approximately two orders of magnitude. Moreover, glutamate-induced toxicity in differentiated cells, but not undifferentiated cells, was inhibited by the N-methyi-D- aspartate receptor antagonists mk-801 and memantine. Evidently, differentiated HT22 cells expressed N-methyI-D-aspartate receptors, while undifferentiated cells did not. Our experimental findings indicated that differentiation is important for immortalized cell lines to render post-mitotic neuronal properties, and that differentiated HT22 neurons represent a better model of hippocampal neurons than undifferentiated cells.

关键词： neural regeneration brain injury HT22 differentiation N-methyI-D-aspartate receptor glutamateexcitatory neurotoxicity mitosis hippocampus neurons mk-801" memantine grants-supportedpaper neuroregeneration

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