Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior
Epilepsy is a chronic neurological disease which is usually associated with psychiatric comorbidities. Depsression and cognition impairment are considered to be the most common psychiatric comorbidities in epilepsy patients. However, the specific contribution of epilepsy made to these psychiatric co...
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doaj-f5f5bffd094645c1a74ee01d7ac63f222020-11-24T23:13:45ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532017-10-011110.3389/fnbeh.2017.00203283282Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like BehaviorXinjian Zhu0Jingde Dong1Bing Han2Rongrong Huang3Aifeng Zhang4Zhengrong Xia5Huanhuan Chang6Jie Chao7Honghong Yao8Department of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Geriatric Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pathology, Medical School of Southeast University, Nanjing, ChinaAnalysis and Test Center of Nanjing Medical University, Nanjing, ChinaNanjing Biomedical Research Institute of Nanjing University, Nanjing, ChinaDepartment of Physiology, Medical School of Southeast University, Nanjing, ChinaDepartment of Pharmacology, Medical School of Southeast University, Nanjing, ChinaEpilepsy is a chronic neurological disease which is usually associated with psychiatric comorbidities. Depsression and cognition impairment are considered to be the most common psychiatric comorbidities in epilepsy patients. However, the specific contribution of epilepsy made to these psychiatric comorbidities remains largely unknown. Here we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling-induced cognitive impairment and depressive-like behavior. Furthermore, we identified that both hippocampal MAPK and PI3K/AKT signaling pathways were activated in response to PTZ kindling, and the increased MAPK and PI3K/AKT signaling activation was paralleled by increased level of reactive oxygen species (ROS) in the hippocampus. However, the PTZ kindling-induced MAPK, PI3K/AKT signaling activities and the ROS level were attenuated by nNOS gene deficiency, suggesting that nNOS may act through ROS-mediated MAPK and PI3K/AKT signaling pathways to trigger cognition deficit and depressive-like behavior in PTZ-kindled mice. Our findings thus define a specific mechanism for chronic epilepsy-induced cognitive impairment and depressive-like behavior, and identify a potential therapeutic target for psychiatric comorbidities in chronic epilepsy patients.http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00203/fullepilepsyneuronal nitric oxide synthasecognitive impairmentdepressive-like behavior |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinjian Zhu Jingde Dong Bing Han Rongrong Huang Aifeng Zhang Zhengrong Xia Huanhuan Chang Jie Chao Honghong Yao |
spellingShingle |
Xinjian Zhu Jingde Dong Bing Han Rongrong Huang Aifeng Zhang Zhengrong Xia Huanhuan Chang Jie Chao Honghong Yao Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior Frontiers in Behavioral Neuroscience epilepsy neuronal nitric oxide synthase cognitive impairment depressive-like behavior |
author_facet |
Xinjian Zhu Jingde Dong Bing Han Rongrong Huang Aifeng Zhang Zhengrong Xia Huanhuan Chang Jie Chao Honghong Yao |
author_sort |
Xinjian Zhu |
title |
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior |
title_short |
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior |
title_full |
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior |
title_fullStr |
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior |
title_full_unstemmed |
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior |
title_sort |
neuronal nitric oxide synthase contributes to ptz kindling-induced cognitive impairment and depressive-like behavior |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Behavioral Neuroscience |
issn |
1662-5153 |
publishDate |
2017-10-01 |
description |
Epilepsy is a chronic neurological disease which is usually associated with psychiatric comorbidities. Depsression and cognition impairment are considered to be the most common psychiatric comorbidities in epilepsy patients. However, the specific contribution of epilepsy made to these psychiatric comorbidities remains largely unknown. Here we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling-induced cognitive impairment and depressive-like behavior. Furthermore, we identified that both hippocampal MAPK and PI3K/AKT signaling pathways were activated in response to PTZ kindling, and the increased MAPK and PI3K/AKT signaling activation was paralleled by increased level of reactive oxygen species (ROS) in the hippocampus. However, the PTZ kindling-induced MAPK, PI3K/AKT signaling activities and the ROS level were attenuated by nNOS gene deficiency, suggesting that nNOS may act through ROS-mediated MAPK and PI3K/AKT signaling pathways to trigger cognition deficit and depressive-like behavior in PTZ-kindled mice. Our findings thus define a specific mechanism for chronic epilepsy-induced cognitive impairment and depressive-like behavior, and identify a potential therapeutic target for psychiatric comorbidities in chronic epilepsy patients. |
topic |
epilepsy neuronal nitric oxide synthase cognitive impairment depressive-like behavior |
url |
http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00203/full |
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