title: Manganese-enhanced magnetic resonance imaging investigation of the interferon-α model of depression in rats.
abstract: Therapeutic effects of interferon-α (IFN-α) are known to be associated with CNS toxicity in humans, and in particular with depression symptoms. Animal models of IFN-α-induced depression (sickness behaviour) have been developed in rodents using various preparations, dosing schedules or routes of administrations. In this work, Manganese Enhanced MRI (MEMRI) has been applied to investigate an experimental model of sickness behaviour induced by administration of IFN-α in rats. IFN-α (3.10(5) U/kg), or vehicle, was daily administered i.p., for 7days in rats (n=20 IFN-α treated and n=20 controls). After treatment, animals were assigned to behavioural (n=10 treated, n=10 control) or MRI (n=10 treated and n=10 control) studies. Animals assigned to the MRI study received two repeated i.p. injections of MnCl2, before image acquisition. Images were acquired at 4.7T using T1 mapping for determination of Mn concentration in brain. After co-registration of T1 maps to a digital brain atlas, differences between brains of treated and untreated animals were assessed pixel-to-pixel by statistical analysis. Behavioural tests showed alterations in freezing and struggling parameters, as expected in an experimental model of sickness behaviour. MRI showed a well defined brain region, mainly contained in the visual cortex, in which Mn uptake was significantly lower in treated than in control animals, indicating probably altered functionality. No significant difference was detected in other brain regions. In addition, a statistically significant decrease in the volume of the pituitary gland, paralleled by a slight increase in its Mn content, was detected in treated animals. MEMRI provides both morphological and functional information in the brain of small laboratory animals and can constitute a valuable tool in the investigation of experimental models of psychiatric diseases.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Daducci
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tambalo
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fiorini
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Osculati
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Teti
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Paolo F
authors.initials: PF
authors.lastname: Fabene
authors.affiliation: Aptuit S.r.l. Center for Drug Discovery & Development, Verona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.affiliation: Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.affiliation: Department of Computer Science, University of Verona, Italy. Electronic address: pasquina.marzola@univr.it.
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
mesh_terms: D000818:Animals; D002712:Chlorides; D003287:Contrast Media; D003863:Depression / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha; D008297:Male; D017895:Manganese Compounds; D001523:Mental Disorders / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D010902:Pituitary Gland / Q000473:pathology* / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002712:Chlorides; D003287:Contrast Media; D016898:Interferon-alpha; D017895:Manganese Compounds; C025340:manganese chloride
keywords: Depression; Interferon-α; MRI; Manganese; Pituitary Gland