White Matter Changes Following Chronic Restraint Stress and Neuromodulation: A Diffusion Magnetic Resonance Imaging Study in Young Male Rats

Bhedita Jaya Seewoo; Kirk Wayne Feindel; Yerim Won; Alexander Clemens Joos; Abbey Figliomeni; Lauren Anne Hennessy; Jennifer Rodger

doi:10.1016/j.bpsgos.2021.08.006

White Matter Changes Following Chronic Restraint Stress and Neuromodulation: A Diffusion Magnetic Resonance Imaging Study in Young Male Rats

Biol Psychiatry Glob Open Sci. 2021 Sep 6;2(2):153-166. doi: 10.1016/j.bpsgos.2021.08.006. eCollection 2022 Apr.

Authors

Bhedita Jaya Seewoo^{1

2

3}, Kirk Wayne Feindel^{2

4}, Yerim Won⁵, Alexander Clemens Joos², Abbey Figliomeni^{1

3

6}, Lauren Anne Hennessy^{1

3}, Jennifer Rodger^{1

3}

Affiliations

¹ Experimental and Regenerative Neurosciences, School of the Biological Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
² Centre for Microscopy, Characterisation & Analysis, Research Infrastructure Centres, The University of Western Australia, Crawley, Western Australia, Australia.
³ Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
⁴ School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
⁵ School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
⁶ School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia.

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation technique, is an effective treatment for depression. However, few studies have used diffusion magnetic resonance imaging to investigate the longitudinal effects of rTMS on the abnormal brain white matter (WM) described in depression.

Methods: In this study, we acquired diffusion magnetic resonance imaging from young adult male Sprague Dawley rats to investigate 1) the longitudinal effects of 10- and 1-Hz low-intensity rTMS (LI-rTMS) in healthy animals; 2) the effect of chronic restraint stress (CRS), an animal model of depression; and 3) the effect of 10 Hz LI-rTMS in CRS animals. Diffusion magnetic resonance imaging data were analyzed using tract-based spatial statistics and fixel-based analysis.

Results: Similar changes in diffusion and kurtosis fractional anisotropy were induced by 10- and 1-Hz stimulation in healthy animals, although changes induced by 10-Hz stimulation were detected earlier than those following 1-Hz stimulation. Additionally, 10-Hz stimulation increased axial and mean kurtosis within the external capsule, suggesting that the two protocols may act via different underlying mechanisms. Brain maturation-related changes in WM, such as increased corpus callosum, fimbria, and external and internal capsule fiber cross-section, were compromised in CRS animals compared with healthy control animals and were rescued by 10-Hz LI-rTMS. Immunohistochemistry revealed increased myelination within the corpus callosum in LI-rTMS-treated CRS animals compared with those that received sham or no stimulation.

Conclusions: Overall, decreased WM connectivity and integrity in the CRS model corroborate findings in patients experiencing depression with high anxiety, and the observed LI-rTMS-induced effects on WM structure suggest that LI-rTMS might rescue abnormal WM by increasing myelination.

Keywords: Animal model; Chronic restraint stress; Depression; Diffusion MRI; Myelin; rTMS.