ArticleFrontiers in behavioral neuroscience2017
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior.
Article in Frontiers in behavioral neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 42 citations in OpenAlex.
- Candidate Serum Biomarkers of Neural Injury and Neuroinflammation in Childhood Epilepsy: Comparison Between Controlled and Drug-Resistant Phenotypes.Children (Basel, Switzerland) · 2026Article
- Kainic acid status epilepticus - induced changes in the hippocampus and hypothalamus alter the effects of exogenous Orexin-A in the hippocampus.IBRO neuroscience reports · 2025Article
- Unraveling the Complex Interplay Between Neuroinflammation and Depression: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Barbaloin Protects Pentylenetetrazol-Induced Cognitive Deficits in Rodents via Modulation of Neurotransmitters and Inhibition of Oxidative-Free-Radicals-Led Inflammation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy.Frontiers in pharmacology · 2024Review
- Role of Inflammation in the Development of COVID-19 to Parkinson's Disease.Journal of inflammation research · 2024Article
- Seizure susceptibility to various convulsant stimuli in the BTBR mouse model of autism spectrum disorders.Frontiers in pharmacology · 2023Article
- Combination of levetiracetam with sodium selenite prevents pentylenetetrazole-induced kindling and behavioral comorbidities in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- A Novel Pathway Phenotype of Temporal Lobe Epilepsy and Comorbid Psychiatric Disorders: Results of Precision Nomothetic Medicine.Antioxidants (Basel, Switzerland) · 2022Article
- The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats.Metabolic brain disease · 2021Article
- Creatine attenuates seizure severity, anxiety and depressive-like behaviors in pentylenetetrazole kindled mice.Metabolic brain disease · 2021Article
- Article
- Simvastatin Improves Behavioral Disorders and Hippocampal Inflammatory Reaction by NMDA-Mediated Anti-inflammatory Function in MPTP-Treated Mice.Cellular and molecular neurobiology · 2020Article
- Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model.Redox biology · 2020Article
- N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Potential neuroprotective and anticonvulsant effects ofFrontiers in neurologyArticle
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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