title: A novel pathogenic mechanism for cerebellar lesions produced by Solanum bonariense in cattle.
abstract: Intoxication with Solanum bonariense in cattle causes cerebellar cortical degeneration with perikaryal vacuolation, axonal swelling, and death primarily of Purkinje cells, with accumulation of electron-dense residual storage bodies in membrane-bound vesicles. The pathogenesis of this disease is not fully understood. Previously, we proposed that inhibition of protein synthesis in Purkinje cells among other altered metabolic pathways could lead to cytoskeletal alterations, subsequently altering cell-specific axonal transport. In the present study, immunohistochemical and histochemical methods were used to identify neuronal cytoskeletal alterations and axonal loss, demyelination, and astrogliosis in the cerebellum of intoxicated bovines. Samples of cerebellum from 3 natural and 4 experimental cases and 2 control bovines were studied. Immunoreactivity against neurofilament (NF)-200KDa confirmed marked loss of Purkinje neurons, and phospho-NF protein, β-tubulin, and affinity reaction against phalloidin revealed an altered perikaryal distribution of neuronal cytoskeletal proteins in the remaining Purkinje cells in intoxicated cattle. Reactive astrogliosis in every layer of the cerebellar cortex was also observed with anti-glial fibrillary acidic protein immunohistochemistry. In affected cattle, demyelination and axonal loss in the cerebellar white matter, as well as basket cell loss were demonstrated with Klüver-Barrera and Bielschowsky stains, respectively. Based on these results, we propose that neuronal cytoskeletal alterations with subsequent interference of the axonal transport in Purkinje cells may play a relevant role in the pathogenesis of this neurodegenerative disorder, and also that demyelination and axonal loss in the cerebellar white matter, as well as astrogliosis in the gray matter, likely occur secondarily to Purkinje cell degeneration and death.
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain jmverdes@fvet.edu.uy.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Verdes
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Márquez
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Aldo
authors.initials: A
authors.lastname: Calliari
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Battes
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Moraña
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Eduardo Juan
authors.initials: EJ
authors.lastname: Gimeno
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Odriozola
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Giannitti
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Florentina
authors.initials: F
authors.lastname: Guerrero
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Luis Eusebio
authors.initials: LE
authors.lastname: Fidalgo
authors.affiliation: Departments of Molecular and Cellular Biology (Biophysics) (Verdes, Calliari, Battes) and Pathology (Verdes, Moraña), Facultad de Veterinaria, Universidad de la República, Montevideo, UruguayDepartment of Proteins and Nucleic Acids, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay (Calliari, Verdes)Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain (Márquez, Pumarola)Institute of Pathology, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina (Gimeno)Estación Experimental Agropecuaria Balcarce, Instituto Nacional de Tecnología Agropecuaria, Balcarce, Argentina (Odriozola)Veterinary Diagnostic Laboratory, Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota and the "Instituto Nacional de Investigación Agropecuaria", La Estanzuela, Colonia, Uruguay (Giannitti)Departments of Anatomy and Animal Production (Guerrero), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, SpainVeterinary Clinical Sciences (Fidalgo), Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D002418:Cattle Diseases / Q000473:pathology*; D002526:Cerebellar Diseases / Q000473:pathology / Q000662:veterinary*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D007150:Immunohistochemistry / Q000662:veterinary; D008297:Male; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000662:veterinary*; D010947:Plants, Toxic; D011689:Purkinje Cells / Q000473:pathology; D032322:Solanum / Q000633:toxicity*
chemical_list: D005904:Glial Fibrillary Acidic Protein
keywords: Bovine; Purkinje cells; Solanum bonariense; cerebellar degeneration; cytoskeletal dysfunction