title: Tin chloride enhances parvalbumin-positive interneuron survival by modulating heme metabolism in a model of cerebral ischemia.
abstract: SnCl(2) has been reported to increase the expression of heme-oxygenase 1 (HO-1), a major antioxidant enzyme, and to decrease ischemic injury, in non-nervous tissues. This study examined the neuroprotective effect of SnCl(2) in the hippocampus of rats submitted to cerebral ischemia. SnCl(2) was administered 18 h before bilateral carotids obstruction. Changes in HO-1 expression and activity, heme content, inducible nitric oxide synthase (iNOS) expression and parvalbumin positive interneuron survival were studied. Thereafter both behavior and memory recovery were tested. The administration of SnCl(2) increased the expression of HO-1 protein and HO activity in the hippocampus and concomitantly decreased heme content at both mitochondrial and nuclear level. Furthermore, ischemized animals showed a strong increase in iNOS expression in the hippocampus, where a loss of parvalbumin positive interneurons also occurred. Pre-treatment with SnCl(2), decreased both iNOS expression in ischemized rats and increased cell survival. The beneficial effects of SnCl(2) were prevented by concomitant treatment with SnMP, a strong inhibitor of HO activity. SnCl(2) also caused an improvement in short term memory recovery. Our results showed that following SnCl(2) administration, HO-1 is strongly induced in the hippocampus and modulate iNOS expression, resulting in a strong neuroprotective effect.
authors.affiliation: Department of Drug Sciences, Section of Biochemistry, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Agata
authors.initials: A
authors.lastname: Zappalà
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Leggio
authors.forename: Carmen
authors.initials: C
authors.lastname: Mazzola
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Francesco
authors.initials: F
authors.lastname: La Delia
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Serapide
authors.forename: Rosalia
authors.initials: R
authors.lastname: Pellitteri
authors.forename: Ignazio
authors.initials: I
authors.lastname: Giannone
authors.forename: Michela
authors.initials: M
authors.lastname: Spatuzza
authors.forename: Valentina
authors.initials: V
authors.lastname: Cicirata
authors.forename: Federico
authors.initials: F
authors.lastname: Cicirata
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D008665:Metalloporphyrins / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017971:Tin Compounds / Q000037:antagonists & inhibitors / Q000627:therapeutic use*
chemical_list: D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D010320:Parvalbumins; D017971:Tin Compounds; C055421:tin mesoporphyrin; C023599:stannous chloride; D006418:Heme; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat