Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model
Abstract Disruption of gamma‐amino butyric acid type A receptors (GABAARs) synaptic clustering and a decrease in the number of GABAARs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12629 |
| _version_ | 1797955814046040064 |
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| author | Xiao‐Lin Zhang Jin‐Yu Zhou Peng Zhang Lan Lin Rong Mei Feng‐Li Zhang Yang‐Mei Chen Rong Li |
| author_facet | Xiao‐Lin Zhang Jin‐Yu Zhou Peng Zhang Lan Lin Rong Mei Feng‐Li Zhang Yang‐Mei Chen Rong Li |
| author_sort | Xiao‐Lin Zhang |
| collection | DOAJ |
| description | Abstract Disruption of gamma‐amino butyric acid type A receptors (GABAARs) synaptic clustering and a decrease in the number of GABAARs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAAR, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)‐induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAAR‐mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ‐induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ‐induced seizures, which was attributed to an increase in the number of GABAARγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti‐seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy. |
| first_indexed | 2024-04-10T23:39:01Z |
| format | Article |
| id | doaj.art-1cca9a2240294f68bcf5dd72cd814b0d |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-04-10T23:39:01Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-1cca9a2240294f68bcf5dd72cd814b0d2023-01-11T10:47:14ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-01-01391616910.1002/kjm2.12629Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy modelXiao‐Lin Zhang0Jin‐Yu Zhou1Peng Zhang2Lan Lin3Rong Mei4Feng‐Li Zhang5Yang‐Mei Chen6Rong Li7Department of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan ChinaDepartment of Rehabilitation Medicine The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan ChinaDepartment of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan ChinaDepartment of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan ChinaDepartment of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan ChinaAbstract Disruption of gamma‐amino butyric acid type A receptors (GABAARs) synaptic clustering and a decrease in the number of GABAARs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAAR, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)‐induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAAR‐mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ‐induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ‐induced seizures, which was attributed to an increase in the number of GABAARγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti‐seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy.https://doi.org/10.1002/kjm2.12629Clptm1epileptic seizureGABAARγ2inhibitory synaptic transmission |
| spellingShingle | Xiao‐Lin Zhang Jin‐Yu Zhou Peng Zhang Lan Lin Rong Mei Feng‐Li Zhang Yang‐Mei Chen Rong Li Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model Kaohsiung Journal of Medical Sciences Clptm1 epileptic seizure GABAARγ2 inhibitory synaptic transmission |
| title | Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model |
| title_full | Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model |
| title_fullStr | Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model |
| title_full_unstemmed | Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model |
| title_short | Clptm1, a new target in suppressing epileptic seizure by regulating GABAAR‐mediated inhibitory synaptic transmission in a PTZ‐induced epilepsy model |
| title_sort | clptm1 a new target in suppressing epileptic seizure by regulating gabaar mediated inhibitory synaptic transmission in a ptz induced epilepsy model |
| topic | Clptm1 epileptic seizure GABAARγ2 inhibitory synaptic transmission |
| url | https://doi.org/10.1002/kjm2.12629 |
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