title: Glial fibrillary acidic protein (GFAP) immunoreactivity correlates with cortical perfusion parameters determined by bolus tracking arterial spin labelling (bt-ASL) magnetic resonance (MR) imaging in the Wistar Kyoto rat.
abstract: Alterations in astrocyte number and function have been implicated in the pathophysiology of a number of psychiatric disorders. The development of magnetic resonance imaging (MRI) as a tool in the animal laboratory has enabled an investigation of the relationship between pathological and neuroimaging markers in animal models. However the physiological processes which underlie these markers and their role in mediating behavioural deficits is still poorly understood. Rodent models have provided us with important insights into physiological and cellular mechanisms which may mediate anxiety and depression-related behaviours. The Wistar-Kyoto (WKY) rat is a strain which endogenously expresses highly anxious and depressive-like behaviours and has previously been reported to exhibit alterations in immunoreactivity for the astrocytic marker glial fibrillary acidic protein (GFAP) in brain sub-regions relative to more stress resilient out-bred strains. Here we report that the depressive and anxiety-like behaviours exhibited by the WKY rat strain are associated with alterations in brain morphology including a decrease in hippocampal volume, coupled with reduced resting state frontal cortical perfusion as assessed by MR bolus tracking arterial spin labelling (bt-ASL) relative to the out-bred Wistar strain. Pre-limbic cortical GFAP immunoreactivity and astrocyte cell number were positively correlated with cortical blood perfusion in the WKY strain. These experiments provide a link between pathological and neuroimaging markers of aberrant astrocytic function and add validity to the WKY rat as a model for co-morbid anxiety and depression.
authors.affiliation: Neuropsychopharmacology Research Group, School of Pharmacy & Pharmaceutical Sciences, Dublin, Ireland. Electronic address: sgormley@tcd.ie.
authors.forename: Shane
authors.initials: S
authors.lastname: Gormley
authors.affiliation: Neuropsychopharmacology Research Group, School of Pharmacy & Pharmaceutical Sciences, Dublin, Ireland; Trinity College Institute of Neuroscience, Dublin, Ireland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rouine
authors.affiliation: Trinity College Institute of Neuroscience, Dublin, Ireland.
authors.forename: Allison
authors.initials: A
authors.lastname: McIntosh
authors.affiliation: Trinity College Institute of Neuroscience, Dublin, Ireland.
authors.forename: Christian
authors.initials: C
authors.lastname: Kerskens
authors.affiliation: Neuropsychopharmacology Research Group, School of Pharmacy & Pharmaceutical Sciences, Dublin, Ireland; Trinity College Institute of Neuroscience, Dublin, Ireland. Electronic address: aharkin@tcd.ie.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harkin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D002452:Cell Count; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000502:physiology; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY / Q000502:physiology*; D017208:Rats, Wistar; D021641:Recognition, Psychology; D013113:Spin Labels; D013550:Swimming / Q000523:psychology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D013113:Spin Labels
keywords: Anxiety; Astrocyte; Depression; Magnetic resonance imaging; Wistar-Kyoto