Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons
Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism - 39(2019), 11 vom: 01. Nov., Seite 2181-2195 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shu, Liang [VerfasserIn] |
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| Links: |
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| Themen: |
Actin Depolymerizing Factors |
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| Anmerkungen: |
Date Completed 16.06.2020 Date Revised 01.11.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/0271678X18785567 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285760696 |
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| 245 | 1 | 0 | |a Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons |
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| 500 | |a Date Revised 01.11.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Middle cerebral artery occlusion | |
| 650 | 4 | |a brain cortex | |
| 650 | 4 | |a cofilin rod | |
| 650 | 4 | |a ischemia | |
| 650 | 4 | |a synaptic dysfunction | |
| 650 | 7 | |a Actin Depolymerizing Factors |2 NLM | |
| 650 | 7 | |a Cofilin 1 |2 NLM | |
| 700 | 1 | |a Chen, Ben |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guoxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yingya |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lidian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yun |e verfasserin |4 aut | |
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