Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus
Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symp...
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2024-11-01
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| author | Yi-Tse Hsiao Ching-Yuan Chang Ting-Yen Lee Wan-Ting Liao Wen-Sung Lai Fang-Chia Chang |
| author_facet | Yi-Tse Hsiao Ching-Yuan Chang Ting-Yen Lee Wan-Ting Liao Wen-Sung Lai Fang-Chia Chang |
| author_sort | Yi-Tse Hsiao |
| collection | DOAJ |
| description | Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. Methods: We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Results: Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Conclusions: Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions. |
| format | Article |
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| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-3db62489bc284f65a165d22dd276d3c22024-11-26T17:55:11ZengMDPI AGBrain Sciences2076-34252024-11-011411115010.3390/brainsci14111150Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal HippocampusYi-Tse Hsiao0Ching-Yuan Chang1Ting-Yen Lee2Wan-Ting Liao3Wen-Sung Lai4Fang-Chia Chang5Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, TaiwanNeurobiology and Cognitive Science Center, National Taiwan University, Taipei 10617, TaiwanDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, TaiwanBackground: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. Methods: We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Results: Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Conclusions: Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions.https://www.mdpi.com/2076-3425/14/11/1150glycineMiniscopecalcium imagingschizophreniahypofunction model |
| spellingShingle | Yi-Tse Hsiao Ching-Yuan Chang Ting-Yen Lee Wan-Ting Liao Wen-Sung Lai Fang-Chia Chang Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus Brain Sciences glycine Miniscope calcium imaging schizophrenia hypofunction model |
| title | Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus |
| title_full | Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus |
| title_fullStr | Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus |
| title_full_unstemmed | Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus |
| title_short | Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus |
| title_sort | effects of sarcosine n methylglycine on nmda n methyl d aspartate receptor hypofunction induced by mk801 in vivo calcium imaging in the ca1 region of the dorsal hippocampus |
| topic | glycine Miniscope calcium imaging schizophrenia hypofunction model |
| url | https://www.mdpi.com/2076-3425/14/11/1150 |
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