title: Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampus.
abstract: Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as status epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na(+)/glucose cotransporters (SGLTs) on hippocampus during SE is still unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after pilocarpine (PILO)-induced SE. Vehicle (VEH, 1μL) or phlorizin, a specific SGLT inhibitor (PZN, 1μL, 50μg/μL), was administered in the hippocampus of rats 30min before PILO (VEH+PILO or PZN+PILO, respectively). The limbic seizures were classified using the Racine's scale, and the amount of wet dog shakes (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade C (FJ-C), and FJ-C-positive neurons (FJ-C+) were counted 24h and 15days after SE. The PZN-treated rats showed higher (p<0.05) number of WDS when compared with VEH+PILO. There was no difference in seizure severity between PZN+PILO and VEH+PILO groups. However, the pattern of limbic seizures significantly changed in PZN+PILO. Indeed, the class 5 seizures repeated themselves more times (p<0.05) than the other classes in the PZN group at 50min after SE induction. The PZN+PILO animals had a higher (p<0.05) number of FJ-C+ cells in the dentate gyrus (DG), hilus, and CA3 and CA1 of hippocampus, when compared with VEH+PILO. The PZN+PILO animals had a decreased number (p<0.05) of FJ-C+ cells in CA1 compared with VEH+PILO 15days after SE induction. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures during SE and increased neurodegeneration in hippocampus 24h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stages of epileptogenic processes.
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Melo
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Yngrid M O
authors.initials: YMO
authors.lastname: Santos
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Maísa A
authors.initials: MA
authors.lastname: Costa
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Amanda L D
authors.initials: ALD
authors.lastname: Pacheco
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Nívea K G T
authors.initials: NKGT
authors.lastname: Silva
authors.affiliation: Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlândia, MG, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Cardoso-Sousa
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, MG, Brazil.
authors.forename: U P
authors.initials: UP
authors.lastname: Pereira
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, MG, Brazil.
authors.forename: L R
authors.initials: LR
authors.lastname: Goulart
authors.affiliation: Physiology Department, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Norberto
authors.initials: N
authors.lastname: Garcia-Cairasco
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Duzzioni
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil.
authors.forename: Daniel L G
authors.initials: DLG
authors.lastname: Gitaí
authors.affiliation: Campus Centro-Oeste Dona Lindu, Federal University of São João del Rei (UFSJ), Divinópolis, MG, Brazil.
authors.forename: Cristiane Q
authors.initials: CQ
authors.lastname: Tilelli
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil; Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlândia, MG, Brazil. Electronic address: robinsonsabino@gmail.com.
authors.forename: Robinson
authors.initials: R
authors.lastname: Sabino-Silva
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceio, AL, Brazil. Electronic address: olagidewww@gmail.com.
authors.forename: Olagide W
authors.initials: OW
authors.lastname: Castro
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010695:Phlorhizin / Q000494:pharmacology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D051247:Sodium-Glucose Transport Proteins; D010862:Pilocarpine; D010695:Phlorhizin
keywords: Fluoro-Jade C; Hippocampus; Neurodegeneration; Phlorizin; Pilocarpine; SGLT1; SGLT2; Status epilepticus