title: Stress-induced alterations in large-scale functional networks of the rodent brain.
abstract: Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10 days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research.
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands. Electronic address: marloes.henckens@weizmann.ac.il.
authors.forename: Marloes J A G
authors.initials: MJ
authors.lastname: Henckens
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Kajo
authors.initials: K
authors.lastname: van der Marel
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: van der Toorn
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Anup G
authors.initials: AG
authors.lastname: Pillai
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D002908:Chronic Disease; D066128:Gray Matter / Q000473:pathology; D020547:Lateral Ventricles / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*
keywords: DKI; Dendritic morphology; Functional connectivity; Rs-fMRI; Stress; Volumetry