Differentiation of HT22 neurons induces expression of NMDA receptor that mediates homocysteine cytotoxicity.


INTRODUCTION: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. MATERIALS AND METHODS: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. RESULTS: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. CONCLUSION: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.


Neurol Res


Neurological research


Zhao Z,Lu R,Zhang B,Shen J,Yang L,Xiao S,Liu J,Suo WZ




Has Abstract


2012-01-01 00:00:00












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  • Dynamical levels of plasma F(1+2) and D-dimer in patients with acute cerebral infarction during intravenous urokinase thrombolysis.

    abstract:OBJECTIVE:To explore the value of dynamically monitored levels of plasma prothrombin fragment(1+2) (F(1+2)) and D-dimer in the process of thrombolysis with urokinase. METHODS:Blood samples were collected at baseline and at hours 1, 2, 3, 6, 12, 24, 48, 72, and 96 after urokinase infusion finished. The levels of plasma...

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    更新日期:2009-05-01 00:00:00

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    更新日期:2020-12-01 00:00:00

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    authors: McCormick PW,Stewart M,Ray P,Lewis G,Dujovny M,Ausman JI

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    pub_type: 临床试验,杂志文章,随机对照试验


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    更新日期:2000-03-01 00:00:00

  • Ramipril prevents extracellular matrix accumulation in cerebral microvessels.

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    authors: Liebetrau M,Burggraf D,Büscher C,Linz W,Hamann GF

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    authors: Smith ML,Counelis GJ,Maloney-Wilensky E,Stiefel MF,Donley K,LeRoux PD

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    pub_type: 临床试验,杂志文章,随机对照试验


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    更新日期:1984-09-01 00:00:00

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    更新日期:2001-09-01 00:00:00

  • Multidisciplinary treatment of posterior circulation ischemia.

    abstract::Compromise of blood flow to the brain leads to cerebral ischemia, which if left untreated may even result in cerebral infarction. This has been the main cause of major morbidity and mortality over the years in the US and around the world. Cerebral ischemia to the posterior fossa is more critical and difficult to treat...

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    authors: Misra M,Alp MS,Hier D,Ausman JI

    更新日期:2004-01-01 00:00:00

  • Peripheral repetitive magnetic stimulation induces intracortical inhibition in healthy subjects.

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    journal_title:Neurological research

    pub_type: 杂志文章


    authors: Krause P,Straube A

    更新日期:2008-09-01 00:00:00

  • Serum leptin is associated with first-ever ischemic stroke, lesion size and stroke severity in a Chinese cohort.

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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