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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Cell Death, Cell Differentiation, Cell Survival, Cells, Cultured, Cytotoxins, Dizocilpine Maleate, Hippocampus, Homocysteine, Memantine, Mice, Neurons, Receptors, N-Methyl-D-Aspartate.
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Does differentiation of HT22 neurons induce expression of NMDA receptor that mediates homocysteine cytotoxicity? Context: Neurotoxic homocysteine (Hcy) is thought to be an independent risk factor for neurodegenerative diseases, including Alzheimer's disease. This study is to determine whether HT22 cells, a murine hippocampal neuronal model, can be used as an  in vitro model, besides the primary neuronal cultures, to investigate the effects of Hcy. MTS assay and Hoechst 33342/propidium iodide discrimination were used to assess the cell viability and cell death on undifferentiated and differentiated HT22 cells.  Semi-quantitative reverse transcription polymerase chain reaction and western blot were used to determine the expression of N-methyl D-aspartate (NMDA) receptor. We found that undifferentiated and differentiated HT22 cells responded to Hcy toxicity differentially, with the  undifferentiated cells resistant while the differentiated cells sensitive. The underlying mechanism appeared to be the differential expression levels of NMDA glutamate receptor between the undifferentiated and differentiated cells. Similar to what have been observed in primary neuronal cultures,  the Hcy toxicity in the differentiated HT22 cells was largely attenuated by NMDA receptor antagonists, MK-801 and memantine.
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These results suggest for the first time that the differentiation of HT22 cells could induce the expression of NMDA receptors, which lead to Hcy  mediate concentration-dependent apoptosis-necrotic continuum of HT22 cell death. The differentiation status of the HT22 cells is important for modeling neurons in vitro, with the differentiated HT22 neurons resembling more characteristics of primary hippocampal neurons while the undifferentiated  HT22 cells being proliferating neuronal precursor cells. The differentiated HT22 neurons can be used as a platform to study Hcy toxicity. Final Decision: yes