Abstract
Chronic mild stress leads to depression in many cases and is linked to several debilitating diseases including mental disorders. Recently, neuronal tracing techniques, stereology, and immunohistochemistry have revealed persistent and significant microstructural alterations in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which form an interconnected system known as the stress circuit. Most studies have focused only on this circuit, however, some studies indicate that manipulation of sensory and motor systems may impact genesis and therapy of mood disorders and therefore these areas should not be neglected in the study of brain microstructure alterations in response to stress and depression. For this reason, we explore the microstructural alterations in different cortical regions in a chronic mild stress model of depression. The study employs ex-vivo diffusion MRI (d-MRI) to assess cortical microstructure in stressed (anhedonic and resilient) and control animals. MRI is followed by immunohistochemistry to substantiate the d-MRI findings. We find significantly lower extracellular diffusivity in auditory cortex (AC) of stress groups and a significantly higher fractional anisotropy in the resilient group. Neurite density was not found to be significantly higher in any cortical ROIs in the stress group compared to control, although axonal density is higher in the stress groups. We also report significant thinning of motor cortex (MC) in both stress groups. This is in agreement with recent clinical and preclinical studies on depression and similar disorders where significant microstructural and metabolic alterations were found in AC and MC. Our findings provide further evidence that the AC and MC are sensitive towards stress exposure and may extend our understanding of the microstructural effects of stress beyond the stress circuit of the brain. Progress in this field may provide new avenues of research to help in diagnosis and treatment intervention for depression and related disorders.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e0192329 |
| Tidsskrift | PLOS ONE |
| Vol/bind | 13 |
| Udgave nummer | 2 |
| ISSN | 1932-6203 |
| DOI | |
| Status | Udgivet - feb. 2018 |
| Udgivet eksternt | Ja |
Bibliografisk note
Funding Information:Lundbeck Foundation grant R83–A7548 supported SNJ and ARK. Simon Fougner Hartmanns Familiefond supported SNJ. AC, ARK, and BH acknowledge support from NIH 1R01EB012874-01. The authors wish to thank Lippert’s Foundation, Korning’s Foundation, and the Augustinus Foundation for financial support. The 9.4T lab was made possible by funding from the Danish Research Counsil’s Infrastructure program, the Velux Foundations, and the Department of Clinical Medicine, AU. Centre for Stochastic Geometry and Advanced Bioimaging is supported by Villum Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2018 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.