Neuropharmacology · 2025
Using in vivo MRI to reveal circuits that are sensitive to traumatic stress in male and female rats.
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Mohammadmirzaei Negin, Kulkarni Praveen, Biddle Matt, Cai Xuezhu, Hekmatyar Khan, Knox Dayan
Аннотация
BACKGROUND: Post traumatic stress disorder (PTSD) is debilitating and more prevalent in women than men. While this suggests there are sex differences in the way neural systems respond to traumatic stress, identifying these systems are challenging. As such, studies designed to identify neural systems that are differentially sensitive to traumatic stress are needed.
METHODS: We examined the impact of traumatic stress within a rat model (single prolonged stress (SPS)) on resting-state functional connectivity (rs-FC) and anatomical volume using in vivo MRI. Rs-FC and anatomical volume were measured before and after application of stress in male and female rats. Algorithmic, clustering, and GLM approaches were used to characterize how SPS changed rs-FC and volume across multiple neural systems.
RESULTS: SPS decreased rs-FC within the DMN, within the hippocampus (Hipp), and increased rs-FC between the thalamus (th) and striatum. Changes in th-Hipp connectivity brought on by SPS were different in males and females, with decreased rs-FC between the mediodorsal thalamus (thMD) and ventral CA1 (vCA1) occurring in males, and increased rs-FC between the paraventricular thalamic nucleus (PV) and vCA1, and thMD and the dorsal dentate gyrus (dDG), occurring in female rats. In control rats dDG volume expanded from the pre-to post-stress scans and this expansion was inhibited in SPS animals.
CONCLUSIONS: The results of this study raise the possibility that sex differences in traumatic stress responsivity could manifest through thalamo-Hipp circuits. The results also raise the possibility that traumatic stress may inhibit natural volumetric expansions within the Hipp.
METHODS: We examined the impact of traumatic stress within a rat model (single prolonged stress (SPS)) on resting-state functional connectivity (rs-FC) and anatomical volume using in vivo MRI. Rs-FC and anatomical volume were measured before and after application of stress in male and female rats. Algorithmic, clustering, and GLM approaches were used to characterize how SPS changed rs-FC and volume across multiple neural systems.
RESULTS: SPS decreased rs-FC within the DMN, within the hippocampus (Hipp), and increased rs-FC between the thalamus (th) and striatum. Changes in th-Hipp connectivity brought on by SPS were different in males and females, with decreased rs-FC between the mediodorsal thalamus (thMD) and ventral CA1 (vCA1) occurring in males, and increased rs-FC between the paraventricular thalamic nucleus (PV) and vCA1, and thMD and the dorsal dentate gyrus (dDG), occurring in female rats. In control rats dDG volume expanded from the pre-to post-stress scans and this expansion was inhibited in SPS animals.
CONCLUSIONS: The results of this study raise the possibility that sex differences in traumatic stress responsivity could manifest through thalamo-Hipp circuits. The results also raise the possibility that traumatic stress may inhibit natural volumetric expansions within the Hipp.