title: Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.
abstract: The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present.
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Thiele
authors.affiliation: Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: T S
authors.initials: TS
authors.lastname: Spehl
authors.affiliation: Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Frings
authors.affiliation: Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Braun
authors.affiliation: Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ferch
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: L L
authors.initials: LL
authors.lastname: Furlanetti
authors.affiliation: Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: P T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: V A
authors.initials: VA
authors.lastname: Coenen
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany. Electronic address: mate.dobrossy@uniklinik-freiburg.de.
authors.forename: M D
authors.initials: MD
authors.lastname: Döbrössy
mesh_terms: D000375:Aging / Q000502:physiology / Q000523:psychology; D000818:Animals; D001931:Brain Mapping; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000000981:diagnostic imaging* / Q000503:physiopathology* / Q000523:psychology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D007859:Learning Disabilities / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D021641:Recognition, Psychology; D065852:Spatial Memory; D013045:Species Specificity
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D003345:Corticosterone
keywords: Animal models; Depression; Entorhinal cortex; Learning/memory; PET; Time dependent behavioral phenotypes