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Neurite atrophy in dorsal hippocampus of rat indicates incomplete recovery of chronic mild stress induced depression
Author(s) -
Khan Ahmad Raza,
Hansen Brian,
Danladi Jibrin,
Chuhutin Andrey,
Wiborg Ove,
Nyengaard Jens R.,
Jespersen Sune Nørhøj
Publication year - 2019
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4057
Subject(s) - fractional anisotropy , diffusion mri , neurite , hippocampus , subiculum , kurtosis , neuroscience , atrophy , medicine , pathology , chemistry , psychology , magnetic resonance imaging , radiology , dentate gyrus , biochemistry , in vitro , statistics , mathematics
Depression is a leading cause of disability worldwide, and it can often ensue after a chronic mild stress (CMS) exposure. Despite intensive preclinical and clinical research, an objective test to diagnose depression is still not available, causing suboptimal diagnosis and treatment. Recently, the neuronal tracing technique and stereology showed persistent microstructural alterations in the stress‐sensitive brain regions, such as dendritic atrophy in the hippocampus (HP) and prefrontal cortex, (PFC) and hypertrophy in the amygdala (AM). These brain regions also showed consistent gliosis in cadaver brains of patients with depressive disorders as well as in the animal model of depression. Clinically feasible methods to probe these microstructural alterations could be useful in treatment planning and intervention. The present study employed ex vivo diffusion MRI (dMRI) and immunohistochemistry to identify microstructural alterations in stress‐sensitive brain regions of CMS‐induced anhedonic rats after eight weeks of spontaneous recovery in comparison with age‐matched controls. The investigation employs dMRI‐based neurite density model parameters ( ν , D eff , and D L ), traditional diffusion kurtosis imaging parameters (mean kurtosis, axial kurtosis, and radial kurtosis), kurtosis tensor parameters (mean kurtosis tensor, W L , and W T ), and diffusion tensor parameters (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The neurite density ( ν ) parameter has shown a significant reduction in dorsal HP in comparison with the control, while immunohistochemistry showed a significant reduction in histological neurite density ( H ν ) in dorsal HP, ventral HP, and AM. H ν also showed significant correlation with ν , which strengthens the reliability of ν and provides a plausible underpinning of the diffusion signal. However, the correlation was not significant when evaluated in the anhedonic group alone. These stress‐recovery findings are opposite to the changes observed just after the CMS exposure paradigm in our recent in vivo study. The present study revealed long‐term effects of CMS exposure, which may be due to incomplete microstructural normalization or long‐lasting microstructural alterations in dHP.