title: Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc.
abstract: Zinc is an essential trace element that is critical for a large number of structural proteins, enzymatic processes and transcription factors. In the brain, zinc ions are involved in synaptic transmission. The homeostasis of zinc is crucial for cell survival and function, and cells have developed a wide variety of systems to control zinc concentration. Alterations in free zinc concentration have been related with brain dysfunction. Down Syndrome individuals present alterations in free zinc concentration and in some of the proteins related with zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating protein metallothionein 3 in the astrocytes using primary cultures of the murine model Ts65Dn. We have observed a higher number of zinc positive spots in the cytoplasm of trisomic astrocytes but a decrease in the total concentration of total intracellular free zinc concentration (including the spots) respect to control astrocytes. Using FM1-43 staining, we found that the endocytic function remains unaltered. Therefore, a possible explanation for this lower concentration of free zinc could be the higher concentration of metallothionein 3 present in the cytoplasm of trisomic astrocytes. The blockade of metallothionein 3 expression using an specific siRNA induced an increase in the concentration of free zinc in basal conditions but failed to increase the uptake of zinc after incubation with zinc ions.
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ballestín
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Blasco-Ibáñez
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Crespo
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Nacher
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: López-Hidalgo
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain; Genetics Department, Universitat de València, INCLIVA, CIBERSAM, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gilabert-Juan
authors.affiliation: Genetics Department, Universitat de València, INCLIVA, CIBERSAM, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Moltó
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, Spain. Electronic address: emilio.varea@uv.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Varea
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D051379:Mice; D008809:Mice, Inbred C3H; D015032:Zinc / Q000378:metabolism*
chemical_list: D015032:Zinc
keywords: Astrocyte; Down Syndrome; Metallothionein 3; TSQ; Ts65Dn; Zinc