Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice
Abstract Background Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor...
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doaj-37c86ef5fc7b44f39d5182cea81a67042021-01-17T12:58:28ZengBMCBMC Neuroscience1471-22022021-01-012211810.1186/s12868-020-00606-zPost-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in miceXin-Ming Luo0Jing Zhao1Wen-Yue Wu2Jie Fu3Zheng-Yu Li4Ming Zhang5Jie Lu6Department of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Neurology, The Second Affiliated Hospital of Nanchang UniversityAbstract Background Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown. Methods In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests. Results We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group. Conclusions These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.https://doi.org/10.1186/s12868-020-00606-zStatus epilepticusFyn inhibitorSaracatinibCognitive functionHippocampal neurons |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin-Ming Luo Jing Zhao Wen-Yue Wu Jie Fu Zheng-Yu Li Ming Zhang Jie Lu |
spellingShingle |
Xin-Ming Luo Jing Zhao Wen-Yue Wu Jie Fu Zheng-Yu Li Ming Zhang Jie Lu Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice BMC Neuroscience Status epilepticus Fyn inhibitor Saracatinib Cognitive function Hippocampal neurons |
author_facet |
Xin-Ming Luo Jing Zhao Wen-Yue Wu Jie Fu Zheng-Yu Li Ming Zhang Jie Lu |
author_sort |
Xin-Ming Luo |
title |
Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice |
title_short |
Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice |
title_full |
Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice |
title_fullStr |
Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice |
title_full_unstemmed |
Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice |
title_sort |
post-status epilepticus treatment with the fyn inhibitor, saracatinib, improves cognitive function in mice |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2021-01-01 |
description |
Abstract Background Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown. Methods In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests. Results We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group. Conclusions These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients. |
topic |
Status epilepticus Fyn inhibitor Saracatinib Cognitive function Hippocampal neurons |
url |
https://doi.org/10.1186/s12868-020-00606-z |
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