Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior

Zhu, Xinjian and Dong, Jingde and Han, Bing and Huang, Rongrong and Zhang, Aifeng and Xia, Zhengrong and Chang, Huanhuan and Chao, Jie and Yao, Honghong (2017) Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior. Frontiers in Behavioral Neuroscience, 11. ISSN 1662-5153

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Abstract

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.

Item Type: Article
Subjects: Euro Archives > Biological Science
Depositing User: Managing Editor
Date Deposited: 18 Feb 2023 06:39
Last Modified: 30 Jan 2024 06:13
URI: http://publish7promo.com/id/eprint/2057

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