title: Functional neuroimaging of amphetamine-induced striatal neurotoxicity in the pleiotrophin knockout mouse model.
abstract: Amphetamine-induced neurotoxic effects have traditionally been studied using immunohistochemistry and other post-mortem techniques, which have proven invaluable for the definition of amphetamine-induced dopaminergic damage in the nigrostriatal pathway. However, these approaches are limited in that they require large numbers of animals and do not provide the temporal data that can be collected in longitudinal studies using functional neuroimaging techniques. Unfortunately, functional imaging studies in rodent models of drug-induced neurotoxicity are lacking. The aim of this study was to evaluate in vivo the changes in brain glucose metabolism caused by amphetamine in the pleiotrophin knockout mouse (PTN-/-), a genetic model with increased vulnerability to amphetamine-induced neurotoxic effects. We showed that administration of amphetamine causes a significantly greater loss of striatal tyrosine hydroxylase content in PTN-/- mice than in wild-type (WT) mice. In addition, [(18)F]-FDG-PET shows that amphetamine produces a significant decrease in glucose metabolism in the striatum and prefrontal cortex in the PTN-/- mice, compared to WT mice. These findings suggest that [(18)F]-FDG uptake measured by PET is useful for detecting amphetamine-induced changes in glucose metabolism in vivo in specific brain areas, including the striatum, a key feature of amphetamine-induced neurotoxicity.
authors.affiliation: Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER de Salud Mental (CIBERSAM), Madrid, Spain. Electronic address: marisa@mce.hggm.es.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Soto-Montenegro
authors.affiliation: Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vicente-Rodríguez
authors.affiliation: Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pérez-García
authors.affiliation: Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gramage
authors.affiliation: Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER de Salud Mental (CIBERSAM), Madrid, Spain; Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.affiliation: Laboratorio de Farmacología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Herradón
mesh_terms: D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D018345:Mice, Knockout; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C066845:pleiotrophin; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D005947:Glucose
keywords: Amphetamine; Midkine; Neurotoxicity; Parkinsons’s disease; Pleiotrophin; [(18)F]-FDG-PET