title: Differentiation renders susceptibility to excitotoxicity in HT22 neurons.
abstract: 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.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China ; Laboratory for Alzheimer's Disease & Aging Research, Veterans Affairs Medical Center, Kansas, MO 64128, USA.
authors.forename: Minchao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China ; Laboratory for Alzheimer's Disease & Aging Research, Veterans Affairs Medical Center, Kansas, MO 64128, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory for Alzheimer's Disease & Aging Research, Veterans Affairs Medical Center, Kansas, MO 64128, USA.
authors.forename: Shaowu
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Laboratory for Alzheimer's Disease & Aging Research, Veterans Affairs Medical Center, Kansas, MO 64128, USA ; Department of Neurology, University of Kansas Medical Center, Kansas, KS 66170, USA ; Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas, KS 66170, USA.
authors.forename: William Z
authors.initials: WZ
authors.lastname: Suo
keywords: HT22; MK-801; N-methyl-D-aspartate receptor; brain injury; differentiation; excitatory neurotoxicity; glutamate; grants-supported paper; hippocampus; memantine; mitosis; neural regeneration; neurons; neuroregeneration