Longitudinal in vivo Diffusion Tensor Imaging Detects Differential Microstructural Alterations in the Hippocampus of Chronic Social Defeat Stress-Susceptible and Resilient Mice

Abstract

Background: Microstructural alterations in the hippocampus may underlie stress-related disorders and stress susceptibility. However, whether these alterations are pre-existing stress vulnerability biomarkers or accumulative results of chronic stress remain unclear. Moreover, examining the whole hippocampus as one unit and ignoring the possibility of a lateralized effect of stress may mask some stress effects and contribute to the heterogeneity of previous findings.Methods: After C57BL/6 mice were exposed to a 10-day chronic social defeat stress (CSDS) paradigm, different stress phenotypes, i.e., susceptible (n = 10) and resilient (n = 7) mice, were discriminated by the behavior of the mice in a social interaction test. With in vivo diffusion tensor imaging (DTI) scans that were conducted both before and after the stress paradigm, we evaluated diffusion properties in the left and right, dorsal (dHi) and ventral hippocampus (vHi) of experimental mice.Results: A significantly lower fractional anisotropy (FA) was found in the right vHi of the susceptible mice prior to the CSDS paradigm than that found in the resilient mice, suggesting that pre-existing microstructural abnormalities may result in stress susceptibility. However, no significant group differences were found in the post-stress FA values of any of the hippocampal regions of interest (ROIs). In addition, mean diffusivity (MD) and radial diffusivity (RD) values were found to be significantly greater only in the right dHi of the resilient group compared to those of the susceptible mice. Furthermore, a significant longitudinal decrease was only observed in the right dHi RD value of the susceptible mice. Moreover, the social interaction (SI) ratio was positively related to post-stress left MD, right dHi MD, and right dHi RD values and the longitudinal right dHi MD percent change. Meanwhile, a negative relationship was detected between the SI ratio and bilateral mean of the post-stress left relative to right vHi FA value, highlighting the important role of right hippocampus in stress-resilience phenotype.Conclusion: Our findings demonstrated different longitudinal microstructural alterations in the bilateral dHi and vHi between stress-susceptible and resilient subgroups and indicated a right-sided lateralized stress effect, which may be useful in the diagnosis and prevention of stress-related disorders as well as their intervention.

Stress-Induced Microstructural Alterations Correlate With the Cognitive Performance of Rats: A Longitudinal in vivo Diffusion Tensor Imaging Study

“…Ex-vivo diffusion MRI and diffusion kurtosis imaging studies documented specific microstructural changes in the hippocampus, amygdala, and several cortical areas of rats exposed to chronic stress (Khan et al, 2016a(Khan et al, ,b, 2018. These findings have been confirmed by a recent in vivo imaging experiment (Liu X. et al, 2018).…”

“…They also observed increased FA in the hypothalamus and hippocampal CA3 and different structural covariance between brain regions in susceptible and resilient mice (Anacker et al, 2016). Others reported on a significantly lower FA in the right ventral hippocampus of the stress-susceptible mice prior to the chronic stress exposure, suggesting that pre-existing microstructural abnormalities may result in stress susceptibility (Liu X. et al, 2018). Another study documented substantial increase (45%) in the volume of the amygdala of a rat strain that is susceptible to the repeated stress procedure (F344 rats; Bourgin et al, 2015).…”

Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress

“…Mean Ϯ SEM. has been associated with alterations in microRNA expression (Muñoz-Llanos et al, 2018) and microstructural alterations in the dorsal hippocampus (Liu et al, 2018). We have recently shown that the dorsal hippocampus expresses fewer NMDA receptors in the extrasynaptic location (Tse et al, 2019).…”

Rodent models of post-traumatic stress disorder: behavioral assessment

“…Integrated with fMRI, these technologies can map the downstream effects of local manipulations on global brain activity [212][213][214] . The neurobiology of stress can also be studied through diffusion tensor imaging 215 , magnetoencephalography 216 , calcium-based fiber photometry 217,218 , and molecular fMRI 214 . Combined with fMRI, these multimodal methods allow researchers to collect complementary and multi-dimensional information across spatiotemporal scales on the same animal.…”