HT22細(xì)胞已經(jīng)被證實(shí)具有膽堿能神經(jīng)元性質(zhì),,能表達(dá)有活性的基本的膽堿能標(biāo)志,,是一種較好的阿爾茨海默病細(xì)胞模型,。
從最初開(kāi)始,,HT22細(xì)胞便作為一種永生化細(xì)胞模型來(lái)使用,,未分化狀態(tài)的HT22細(xì)胞特性已經(jīng)被研究得較為充分,。2009年有人第一次研究分化后的HT22細(xì)胞的特性:更加接近于成熟神經(jīng)元,,具有更長(zhǎng)更豐富的軸突突起,顯示出更多有功能的膽堿能性質(zhì),。
美國(guó)退伍軍人醫(yī)療中心阿爾茨海默病和老化研究實(shí)驗(yàn)室的William Z. Suo教授領(lǐng)導(dǎo)的研究團(tuán)隊(duì)的一項(xiàng)關(guān)于“Differentiation renders susceptibility to excitotoxicity in HT22 neurons”的研究報(bào)告顯示,,谷氨酸誘導(dǎo)毒性的敏感性在未分化和已分化的HT22細(xì)胞有顯著差異,已分化HT22細(xì)胞表達(dá)N-甲基-D-天門冬氨酸受體,,對(duì)興奮性毒性更敏感,是海馬神經(jīng)元更好的模型,。研究發(fā)表在2013年5月第14期的《中國(guó)神經(jīng)再生研究(英文版)》雜志中,。
(生物谷Bioon.com)
doi:10.3969/j.issn.1673-5374.2013.14.006
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Differentiation renders susceptibility to excitotoxicity in HT22 neurons
Minchao He1, 2, Jun Liu1, 2, Shaowu Cheng2, Yigang Xing1, William Z Suo2, 3, 4
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-methyl-D- aspartate receptor antagonists MK-801 and memantine. Evidently, differentiated HT22 cells expressed N-methyl-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.