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Article

The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy

by
Zhen Li
1,†,
Biying Ge
1,2,†,
Haoqi Li
1,
Chunyao Huang
1,
Yunhan Ji
1,
Melitta Schachner
3,
Shengming Yin
1,4,
Sheng Li
1,5,* and
Jie Zhao
1,4,*
1
National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China
2
Functional Laboratory, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
3
Department of Cell Biology and Neuroscience, Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
4
Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
5
Department of Biochemistry, School of Basic Medical Science, Dalian Medical University, Dalian 116044, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2025, 15(7), 1032; https://doi.org/10.3390/biom15071032
Submission received: 4 May 2025 / Revised: 8 July 2025 / Accepted: 9 July 2025 / Published: 17 July 2025
(This article belongs to the Section Molecular Medicine)
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Abstract

Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms.
Keywords: scorpion venom; peptide; SVHRSP; TLE; L1CAM; cell adhesion molecule; neuroprotection scorpion venom; peptide; SVHRSP; TLE; L1CAM; cell adhesion molecule; neuroprotection

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MDPI and ACS Style

Li, Z.; Ge, B.; Li, H.; Huang, C.; Ji, Y.; Schachner, M.; Yin, S.; Li, S.; Zhao, J. The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy. Biomolecules 2025, 15, 1032. https://doi.org/10.3390/biom15071032

AMA Style

Li Z, Ge B, Li H, Huang C, Ji Y, Schachner M, Yin S, Li S, Zhao J. The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy. Biomolecules. 2025; 15(7):1032. https://doi.org/10.3390/biom15071032

Chicago/Turabian Style

Li, Zhen, Biying Ge, Haoqi Li, Chunyao Huang, Yunhan Ji, Melitta Schachner, Shengming Yin, Sheng Li, and Jie Zhao. 2025. "The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy" Biomolecules 15, no. 7: 1032. https://doi.org/10.3390/biom15071032

APA Style

Li, Z., Ge, B., Li, H., Huang, C., Ji, Y., Schachner, M., Yin, S., Li, S., & Zhao, J. (2025). The Upregulation of L1CAM by SVHRSP Mitigates Neuron Damage, Spontaneous Seizures, and Cognitive Dysfunction in a Kainic Acid-Induced Rat Model of Epilepsy. Biomolecules, 15(7), 1032. https://doi.org/10.3390/biom15071032

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