Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy
Childhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in ~30% of patients while adverse neurological sequel...
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MDPI AG
2023-01-01
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| Loạt: | Biomolecules |
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| Truy cập trực tuyến: | https://www.mdpi.com/2218-273X/13/1/186 |
| _version_ | 1827628125703372800 |
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| author | Muhammad Hassan David R. Grattan Beulah Leitch |
| author_facet | Muhammad Hassan David R. Grattan Beulah Leitch |
| author_sort | Muhammad Hassan |
| collection | DOAJ |
| description | Childhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in ~30% of patients while adverse neurological sequelae remain common. Impaired GABAergic neurotransmission is commonly reported in research models investigating these mechanisms. Recently, we reported a region-specific reduction in the whole-tissue and synaptic GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) α1 subunit and an increase in whole-tissue GAD65 in the primary somatosensory cortex (SoCx) of the adult epileptic stargazer mouse compared with its non-epileptic (NE) littermate. The current study investigated whether these changes occurred prior to the onset of seizures on postnatal days (PN) 17–18, suggesting a causative role. Synaptic and cytosolic fractions were biochemically isolated from primary SoCx lysates followed by semiquantitative Western blot analyses for GABA<sub>A</sub>R α1 and GAD65. We found no significant changes in synaptic GABA<sub>A</sub>R α1 and cytosolic GAD65 in the primary SoCx of the stargazer mice at the critical developmental stages of PN 7–9, 13–15, and 17–18. This indicates that altered levels of GABA<sub>A</sub>R α1 and GAD65 in adult mice do not directly contribute to the initial onset of absence seizures but are a later consequence of seizure activity. |
| first_indexed | 2024-03-09T13:26:23Z |
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| id | doaj.art-8478c7356b774b3babcad2e0d58d2fda |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:26:23Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8478c7356b774b3babcad2e0d58d2fda2023-11-30T21:24:00ZengMDPI AGBiomolecules2218-273X2023-01-0113118610.3390/biom13010186Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence EpilepsyMuhammad Hassan0David R. Grattan1Beulah Leitch2Department of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New ZealandDepartment of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New ZealandDepartment of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New ZealandChildhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in ~30% of patients while adverse neurological sequelae remain common. Impaired GABAergic neurotransmission is commonly reported in research models investigating these mechanisms. Recently, we reported a region-specific reduction in the whole-tissue and synaptic GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) α1 subunit and an increase in whole-tissue GAD65 in the primary somatosensory cortex (SoCx) of the adult epileptic stargazer mouse compared with its non-epileptic (NE) littermate. The current study investigated whether these changes occurred prior to the onset of seizures on postnatal days (PN) 17–18, suggesting a causative role. Synaptic and cytosolic fractions were biochemically isolated from primary SoCx lysates followed by semiquantitative Western blot analyses for GABA<sub>A</sub>R α1 and GAD65. We found no significant changes in synaptic GABA<sub>A</sub>R α1 and cytosolic GAD65 in the primary SoCx of the stargazer mice at the critical developmental stages of PN 7–9, 13–15, and 17–18. This indicates that altered levels of GABA<sub>A</sub>R α1 and GAD65 in adult mice do not directly contribute to the initial onset of absence seizures but are a later consequence of seizure activity.https://www.mdpi.com/2218-273X/13/1/186GABA<sub>A</sub> receptorcortico-thalamocortical networkabsence epilepsyabsence seizuresprimary somatosensory cortexstargazer mouse |
| spellingShingle | Muhammad Hassan David R. Grattan Beulah Leitch Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy Biomolecules GABA<sub>A</sub> receptor cortico-thalamocortical network absence epilepsy absence seizures primary somatosensory cortex stargazer mouse |
| title | Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy |
| title_full | Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy |
| title_fullStr | Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy |
| title_full_unstemmed | Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy |
| title_short | Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy |
| title_sort | developmental inhibitory changes in the primary somatosensory cortex of the stargazer mouse model of absence epilepsy |
| topic | GABA<sub>A</sub> receptor cortico-thalamocortical network absence epilepsy absence seizures primary somatosensory cortex stargazer mouse |
| url | https://www.mdpi.com/2218-273X/13/1/186 |
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