2. Academic Validation
  3. H2S inhibits LiCl/pilocarpine-induced seizures and promotes neuroprotection by regulating TRPV2 expression via the AC3/cAMP/PKA pathway

H2S inhibits LiCl/pilocarpine-induced seizures and promotes neuroprotection by regulating TRPV2 expression via the AC3/cAMP/PKA pathway

  • Neurochem Int. 2024 Jan 28:174:105677. doi: 10.1016/j.neuint.2024.105677.
Jigao Feng 1,  Shenghua Zhuo 2,  Dayuan Liu 3,  Hao Peng 4,  Dachuang Guo 5,  Ning Li 3,  Hu Sun 3,  Caicai Zhang 6,  Jiannong Zhao 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, the Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China; Department of Neurosurgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.
  • 2 Department of Neurosurgery, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
  • 3 Department of Neurosurgery, the Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
  • 4 Department of Neurosurgery, the Second People's Hospital of Hainan Province, Haikou, Hainan, China.
  • 5 Department of Neurosurgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.
  • 6 Department of Physiology, Hainan Medical University, Haikou, Hainan, China. Electronic address: hy0206101@hainmc.edu.cn.
  • 7 Department of Neurosurgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China. Electronic address: zhaojiannong@hainmc.edu.cn.
PMID: 38290616 DOI: 10.1016/j.neuint.2024.105677
Abstract

It is widely acknowledged that epilepsy is a neurological disorder characterized by recurrent and atypical neuronal discharges, resulting in transient dysfunction within the brain. The protective role of hydrogen sulfide (H2S) in epilepsy has been elucidated by recent studies, but the underlying mechanisms remain poorly understood. To investigate this, the concentration of H2S was measured by spectrophotometry and a fluorescent probe in LiCl/Pilocarpine (LiCl/Pilo)-induced seizures in rats. The localization of proteins was examined using immunofluorescence. Electroencephalogram and behavioral tests were employed to evaluate the occurrence of seizures. Neuropathological changes in the hippocampus were examined by hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy. Through proteomics and bioinformatics analysis, we identified the differential proteins in the hippocampus of rats following H2S intervention. Protein changes were detected through western blotting. The results showed that H2S treatment significantly alleviated seizures and minimized post-seizures neurological damage in rats. Proteomics analysis revealed Adenylate Cyclase 3 (AC3) as a protein potentially targeted by H2S. Moreover, the AC3 activator forskolin reversed the downregulation effect of H2S on the AC3/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/transient receptor potential vanilloid 2 (TRPV2) signaling pathway. In conclusion, H2S targets and downregulates the expression of AC3, thereby modulating the AC3/cAMP/PKA signaling pathway to regulate the expression of TRPV2 in LiCl/Pilo-induced seizures, ultimately leading to seizure inhibition and neuroprotection.

Keywords

AC3; H(2)S; PKA; Seizures; TRPV2; cAMP.

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