5-Hydroxytryptamine 6 Receptor Antagonism Ameliorates Depression-Like Behaviors in Temporal Lobe Epilepsy Rats with Potential Involvement of the MEF2C/NF-κB Pathway.
8 affiliations
- 1Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu Province, China.
- 2Department of Cognitive Neuroscience, Donders Institute for Brain, Radboud University Medical Center, Cognition, and Behavior, 6525 EN, Nijmegen, Netherlands.
- 3Department of Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
- 4Department of Dentistry, Orthodontics and Craniofacial Biology, Research Institute for Medical Innovation, Radboud University Medical Center, 6525EX, Nijmegen, Netherlands.
- 5Han University of Applied Sciences, 6524 TM, Nijmegen, Netherlands.
- 6Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu Province, China. [email protected].
- 7Comprehensive Cancer Center of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, Jiangsu Province, China. [email protected].
- 8Department of Radiotherapy, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. [email protected].
Abstract
This study aimed to investigate whether 5-HT6 receptor (5-HT6R) antagonism could ameliorate epilepsy-associated emotional and behavioral disturbances in rats with temporal lobe epilepsy (TLE) and to explore its potential association with the MEF2C/NF-κB pathway. Thirty rats were randomly divided into normal control (NC) group, Model group and 5-HT6R group. The TLE model was established using lithium chloride-pilocarpine. The rats in 5-HT6R group were treated with 5-HT6R antagonist SB271046. Behavioral tests were conducted to evaluate anxiety- and depression-like behaviors associated with epilepsy. Levels of inflammatory factors, 5-HT and KYN in hippocampal tissues were detected by enzyme-linked immunosorbent assay. Neuronal cell death in brain tissues was assessed by TUNEL staining, and the protein expressions of MEF2C and NF-κB p65 were measured by Western blotting. Molecular docking between SB271046 and MEF2C/NF-κB p65 was performed using AutoDock 4. In addition, JASPAR database was used to analyze the putative binding of CREB1 to MEF2C promoter. Rats in the Model group exhibited significant epilepsy-associated anxiety- and depression-like behaviors, accompanied by aggravated inflammation, decreased MEF2C protein expression and increased NF-κB p65 protein expression. Treatment with SB271046 significantly ameliorated these behavioral abnormalities and inflammatory responses, and was associated with upregulated MEF2C protein expression and downregulated NF-κB p65 protein expression. KEGG enrichment analysis suggested the involvement of NF-κB pathway in TLE. Molecular docking revealed potential interactions between SB271046 and MEF2C/NF-κB p65. 5-HT6R antagonist SB271046 may alleviate epilepsy-associated emotional and cognitive disturbances, potentially through neurostabilizing and anti-inflammatory effects linked to modulation of the MEF2C/NF-κB pathway. These mechanistic associations remain preliminary and warrant further validation using targeted gain- or loss-of-function approaches.
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BibTeX
@article{xu20265hydroxytryptamine,
title = {{5-Hydroxytryptamine 6 Receptor Antagonism Ameliorates Depression-Like Behaviors in Temporal Lobe Epilepsy Rats with Potential Involvement of the MEF2C/NF-κB Pathway.}},
author = {Yi-Fan Xu and Ling Shan and Zhi-Hao Wang and Meng-Han Sun and Ling-Ling Mai and Thijs Lodder and Qi-Si Zheng and Bin Huang},
journal = {Cellular and molecular neurobiology},
year = {2026},
month = jul,
doi = {10.1007/s10571-026-01764-0},
url = {https://europepmc.org/article/MED/42911284},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 5-Hydroxytryptamine 6 Receptor Antagonism Ameliorates Depression-Like Behaviors in Temporal Lobe Epilepsy Rats with Potential Involvement of the MEF2C/NF-κB Pathway.
AU - Yi-Fan Xu
AU - Ling Shan
AU - Zhi-Hao Wang
AU - Meng-Han Sun
AU - Ling-Ling Mai
AU - Thijs Lodder
AU - Qi-Si Zheng
AU - Bin Huang
PY - 2026
DA - 2026/07/27
JO - Cellular and molecular neurobiology
DO - 10.1007/s10571-026-01764-0
UR - https://europepmc.org/article/MED/42911284
AB - This study aimed to investigate whether 5-HT6 receptor (5-HT6R) antagonism could ameliorate epilepsy-associated emotional and behavioral disturbances in rats with temporal lobe epilepsy (TLE) and to explore its potential association with the MEF2C/NF-κB pathway. Thirty rats were randomly divided into normal control (NC) group, Model group and 5-HT6R group. The TLE model was established using lithium chloride-pilocarpine. The rats in 5-HT6R group were treated with 5-HT6R antagonist SB271046. Behavioral tests were conducted to evaluate anxiety- and depression-like behaviors associated with epilepsy. Levels of inflammatory factors, 5-HT and KYN in hippocampal tissues were detected by enzyme-linked immunosorbent assay. Neuronal cell death in brain tissues was assessed by TUNEL staining, and the protein expressions of MEF2C and NF-κB p65 were measured by Western blotting. Molecular docking between SB271046 and MEF2C/NF-κB p65 was performed using AutoDock 4. In addition, JASPAR database was used to analyze the putative binding of CREB1 to MEF2C promoter. Rats in the Model group exhibited significant epilepsy-associated anxiety- and depression-like behaviors, accompanied by aggravated inflammation, decreased MEF2C protein expression and increased NF-κB p65 protein expression. Treatment with SB271046 significantly ameliorated these behavioral abnormalities and inflammatory responses, and was associated with upregulated MEF2C protein expression and downregulated NF-κB p65 protein expression. KEGG enrichment analysis suggested the involvement of NF-κB pathway in TLE. Molecular docking revealed potential interactions between SB271046 and MEF2C/NF-κB p65. 5-HT6R antagonist SB271046 may alleviate epilepsy-associated emotional and cognitive disturbances, potentially through neurostabilizing and anti-inflammatory effects linked to modulation of the MEF2C/NF-κB pathway. These mechanistic associations remain preliminary and warrant further validation using targeted gain- or loss-of-function approaches.
SN - 0272-4340
SN - 1573-6830
ER -