Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network

• Published in: Scientific reports 2021-04, Vol.11 (1), p.8252-8252, Article 8252
• Main Authors: Sadeghi, Leila, Rizvanov, Albert Anatolyevich, Dabirmanesh, Bahareh, Salafutdinov, Ilnur Ildusovich, Sayyah, Mohammad, Shojaei, Amir, Zahiri, Javad, Mirnajafi-Zadeh, Javad, Khorsand, Babak, Khajeh, Khosro, Fathollahi, Yaghoub
• Format: Article
• Language: English
• Subjects: 631/378/1689; 631/45/882; Adenosine diphosphate; ADP-ribosyl cyclase; ADP-ribosyl Cyclase - metabolism; Animal models; Animals; Calcium; Calcium - metabolism; Calcium homeostasis; Calcium influx; Calreticulin; Convulsions & seizures; Cyclic ADP-ribose; Cyclic ADP-Ribose - analogs & derivatives; Cyclic ADP-Ribose - physiology; Disease Models, Animal; Electrophoresis - methods; Epilepsy; Epilepsy - genetics; Epilepsy - metabolism; Epilepsy - therapy; Hippocampus; Hippocampus - metabolism; Homeostasis; Humanities and Social Sciences; Hydrolase; Immunohistochemistry; Ions; Kindling; Kindling, Neurologic; Lysophosphatidic acid; Male; Mass spectrometry; Mass spectroscopy; Molecular Targeted Therapy; multidisciplinary; Pilocarpine; Proteins; Proteomics; Rats; Rats, Wistar; Receptors, Lysophosphatidic Acid - metabolism; Ribose; Science; Science (multidisciplinary); Seizures; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Synaptosomal-Associated Protein 25 - metabolism; Ubiquitin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-87555-7

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca 2+ homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments.