Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β (Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether se...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/2123748 |
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| author | Sung-Soo Jang Sara E. Royston Gunhee Lee Shuwei Wang Hee Jung Chung |
| author_facet | Sung-Soo Jang Sara E. Royston Gunhee Lee Shuwei Wang Hee Jung Chung |
| author_sort | Sung-Soo Jang |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β (Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aβ-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aβ levels were observed at 3-4 days following a single ECS when STEP61 level returned to the baseline. Given that pathologic levels of Aβ increase STEP61 activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61 and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aβ expression may contribute to the maintenance of this synaptic weakening. |
| format | Article |
| id | doaj-art-740f85f060fd411bb493d0103e8ca34d |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-740f85f060fd411bb493d0103e8ca34d2025-02-03T01:00:00ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/21237482123748Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic PlasticitySung-Soo Jang0Sara E. Royston1Gunhee Lee2Shuwei Wang3Hee Jung Chung4Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USANeuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USAAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β (Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aβ-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aβ levels were observed at 3-4 days following a single ECS when STEP61 level returned to the baseline. Given that pathologic levels of Aβ increase STEP61 activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61 and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aβ expression may contribute to the maintenance of this synaptic weakening.http://dx.doi.org/10.1155/2016/2123748 |
| spellingShingle | Sung-Soo Jang Sara E. Royston Gunhee Lee Shuwei Wang Hee Jung Chung Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity Neural Plasticity |
| title | Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity |
| title_full | Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity |
| title_fullStr | Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity |
| title_full_unstemmed | Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity |
| title_short | Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity |
| title_sort | seizure induced regulations of amyloid β step61 and step61 substrates involved in hippocampal synaptic plasticity |
| url | http://dx.doi.org/10.1155/2016/2123748 |
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