title: Magnetic resonance imaging and spectroscopy reveal differential hippocampal changes in anhedonic and resilient subtypes of the chronic mild stress rat model.
abstract: BACKGROUND
  Repeated exposure to mild stressors induces anhedonia-a core symptom of major depressive disorder-in up to 70% of the stress-exposed rats, whereas the remaining show resilience to stress. This chronic mild stress (CMS) model is well documented as an animal model of major depressive disorder. We examined the morphological, microstructural, and metabolic characteristics of the hippocampus in anhedonic and stress resilient rats that may mark the differential behavioral outcome.
  
  
  METHODS
  Anhedonic (n = 8), resilient (n = 8), and control (n = 8) rats were subjected to in vivo diffusion kurtosis imaging, high-resolution three-dimensional magnetic resonance imaging and proton magnetic resonance spectroscopy.
  
  
  RESULTS
  Diffusion kurtosis parameters were decreased in both CMS-exposed groups. A significant inward displacement in the ventral part of the right hippocampus was apparent in the resilient subjects and an increase of the glutamate:total creatine ratio and N-acetylaspartylglutamate:total creatine was observed in the anhedonic subjects.
  
  
  CONCLUSIONS
  Diffusion kurtosis imaging discloses subtle substructural changes in the hippocampus of CMS-exposed animals irrespective of their anhedonic or resilient nature. In contrast, proton magnetic resonance spectroscopy and magnetic resonance imaging-based shape change analysis of the hippocampus allowed discrimination of these two subtypes of stress sensitivity. Although the precise mechanism discriminating their behavior is yet to be elucidated, the present study underlines the role of the hippocampus in the etiology of depression and the induction of anhedonia. Our results reflect the potency of noninvasive magnetic resonance methods in preclinical settings with key translational benefit to and from the clinic.
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium. Rafael.Delgadoypalacios@ua.ac.be
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado y Palacios
authors.forename: Adriaan
authors.initials: A
authors.lastname: Campo
authors.forename: Kim
authors.initials: K
authors.lastname: Henningsen
authors.forename: Marleen
authors.initials: M
authors.lastname: Verhoye
authors.forename: Dirk
authors.initials: D
authors.lastname: Poot
authors.forename: Jouke
authors.initials: J
authors.lastname: Dijkstra
authors.forename: Johan
authors.initials: J
authors.lastname: Van Audekerke
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
authors.forename: Jan
authors.initials: J
authors.lastname: Sijbers
authors.forename: Ove
authors.initials: O
authors.lastname: Wiborg
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods; D002452:Cell Count / Q000379:methods; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000145:classification / Q000378:metabolism / Q000473:pathology*