HT22细胞已经被证实具有胆碱能神经元性质，能表达有活性的基本的胆碱能标志，是一种较好的阿尔茨海默病细胞模型。
从最初开始，HT22细胞便作为一种永生化细胞模型来使用，未分化状态的HT22细胞特性已经被研究得较为充分。2009年有人第一次研究分化后的HT22细胞的特性：更加接近于成熟神经元，具有更长更丰富的轴突突起，显示出更多有功能的胆碱能性质。
美国退伍军人医疗中心阿尔茨海默病和老化研究实验室的William Z. Suo教授领导的研究团队的一项关于“Differentiation renders susceptibility to excitotoxicity in HT22 neurons”的研究报告显示，谷氨酸诱导毒性的敏感性在未分化和已分化的HT22细胞有显著差异，已分化HT22细胞表达N-甲基-D-天门冬氨酸受体，对兴奋性毒性更敏感，是海马神经元更好的模型。研究发表在2013年5月第14期的《中国神经再生研究（英文版）》杂志中。
（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.
