High dose corticosterone immediately after stress exposure prevents hippocampal cytoarchitecture and neuronal plasticity damage in an animal model of PTSD

European Journal of Psychotraumatology

关键词: PTSD;    stress;    corticosterone;    neuronal plasticity;    hippocampus;   

DOI  :  10.3402/ejpt.v3i0.19364

来源: DOAJ

【 摘 要 】

Rationale: In a previous study, we examined the effect of a single intervention with high-dose corticosterone, 1h after predator stress-exposure (PSS), and showed a significant reduction in the incidence of PTSD-like behaviors and improved resilience. The underlying mechanism of corticosterone action remains largely unclear. The goal of this study was to explore the cytoarchitecture and molecular changes in hippocampal subareas of animals “treated” with high-dose corticosterone immediately after exposure. Methods: Animals were exposed to PSS and treated 1 hour later with corticosterone (25mg/kg) or saline. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 7 days after the exposure. Pre-set cut-off behavioral criteria classified exposed animals according to behavioral responses as those with “extreme behavioral response”, “minimal behavioral response”, or “intermediate response”. Dendritic arborization in Golgi-impregnated neurons in hippocampal areas was evaluated. Given the importance of integrin 1β, calcium/calmodulin-dependent protein kinase II (CAMKII), phospho-glutamate receptor 1 (pGLU-R1), and postsynaptic density-95 (PSD-95) in neuronal function and dendritic spine plasticity, the expression of these factors in the hippocampus was also examined. Results: Stress exposure altered the morphology of the hippocampal dendritic cells selectively in individuals whose behavior was extremely disrupted (EBR) in response to the exposure, whereas animals whose behavior was less severely affected displayed no significant changes in hippocampi morphology. Extreme responders clearly demonstrated significantly reduced dendritic arbor and spine density along hippocampal dendrites 8 days after exposure. The results showed that EBR animals displayed significantly lower levels of integrin 1β, CAMKII and higher expression of pGLU-R1 and PSD-95 than vehicle-treated animals. In contrast, steroid-treated stressed animals displayed significantly increased dendritic arbor and spine density, with increased levels of integrin 1β, pCAMKII, and obtunded pGLU-R1 and PSD-95 levels. Conclusions: The data provide initial evidence that a single dose of corticosterone administered in the acute aftermath of stress promotes recovery while promoting enhanced neuronal and synaptic plasticity and connectivity in the secondary prevention of PTSD.