title: Naringin attenuates granule cell dispersion in the dentate gyrus in a mouse model of temporal lobe epilepsy.
abstract: Morphological abnormalities of the dentate gyrus (DG) are an important phenotype in the hippocampus of patients with temporal lobe epilepsy. We recently reported that naringin, a bioflavonoid in grapefruit and citrus fruits, exerts beneficial effects in the kainic acid (KA) mouse model of epilepsy. We found that naringin treatment reduced seizure activities and decreased autophagic stress and neuroinflammation in the hippocampus following in vivo lesion with KA. However, it remains unclear whether naringin may also attenuate seizure-induced morphological changes in the DG, collectively known as granule cell dispersion (GCD). To clarify whether naringin treatment reduces GCD, we evaluated the effects of intraperitoneal injection of naringin on GCD and activation of mammalian target of rapamycin complex 1 (mTORC1), an important regulator of GCD, following intrahippocampal injection of KA. Our results showed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which was confirmed by assessing the phosphorylated form of the mTORC1 substrate, 4E-BP1, in the hippocampus. These results suggest that naringin treatment may help prevent epilepsy-induced hippocampal injury by inhibiting mTORC1 activation and thereby reducing GCD in the hippocampus in vivo.
authors.affiliation: School of Life Sciences, Republic of Korea; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Hannah
authors.initials: H
authors.lastname: Jang
authors.affiliation: School of Life Sciences, Republic of Korea. Electronic address: greenquest81@gmail.com.
authors.forename: Kyoung Hoon
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: School of Life Sciences, Republic of Korea; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea. Electronic address: srk75@knu.ac.kr.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D039642:Eukaryotic Initiation Factors; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D044950:Flavanones; D005419:Flavonoids; D010750:Phosphoproteins; D000076222:Mechanistic Target of Rapamycin Complex 1; C005274:naringin; D007608:Kainic Acid
keywords: Dentate gyrus; Granule cell dispersion; Kainic acid; Mammalian target of rapamycin complex 1; Naringin