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Publications

Journal Article Epublish

PubMed: 40723903 DOI: 10.3390/biom15071032

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)

Authors: Zhen Li, Biying Ge, Haoqi Li, Chunyao Huang, Yunhan Ji, Melitta Schachner, Shengming Yin, Sheng Li, Jie Zhao

Affiliations

  • National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China.
  • National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China. Functional Laboratory, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
  • Department of Cell Biology and Neuroscience, Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
  • National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China. Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
  • National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China. Department of Biochemistry, School of Basic Medical Science, Dalian Medical University, Dalian 116044, China.

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.

MeSH

Up-Regulation, Epilepsy, Kainic Acid, Neurons, Cell Adhesion Molecules, Neuroprotection, Cognitive Dysfunction, Axons, Seizures, Therapeutics, Scorpion Venoms, Neural Cell Adhesion Molecule L1