Abstract
The molecular mechanism of fear memory is poorly understood. Therefore, the pathogenesis of post-traumatic stress disorder (PTSD), whose symptom presentation can enhance fear memory, remains largely unclear. Recent studies with knockout animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits acquisition and promotes memory extinction, whereas stathmin regulates innate and basal fear. The aim of our study was to examine changes in the expression of Rin1 and stathmin in different animal models of stress, particluarly traumatic stress. We used three animal traumatic stresses: single prolonged stress (SPS, which is a rodent model of PTSD), an immobilization-stress (IM) and a Loud sound stress (LSS), to examine the change and uniqueness in Rin1/stathmin expression. Behavioral tests of SPS rats demonstrated increased anxiety and contextual fear-conditioning. They showed decreased long-term potentiation (LTP), as well as decreased stathmin and increased Rin1 expression in the hippocampus and the amygdala. Expression of the stathmin effector, tubulin, and downstream molecules Rin1, Rab5, and Abl, appeared to increase. Rin1 and EphA4 were endogenously coexpressed in primary neurons after SPS stimulation. IM rats exhibited increased anxiety behavior and enhanced fear-conditioning to contextual and auditory stimuli. Similar changes in expression of Rin1/stathmin were observed in IM rats whereas no changes were observed in rats exposed to a loud sound. These data suggest that changes in expression of the Rin1 and stathmin genes may be involved in rodents with SPS and IM stresses, which provide valuable insight into fear memories under abnormal conditions, particularly in PTSD.
Highlights
Stathmin, which is called oncoprotein 18, is a neuronal growth-associated protein that is highly expressed in the lateral nucleus of the amygdala and related thalamic and cortical structures (Shumyatsky et al, 2002)
In the open field (OF) test, the rats were placed in a novel environment and they naturally avoided the open space in the center
The results showed no significant differences in time or distance in the closed arms
Summary
Stathmin, which is called oncoprotein 18, is a neuronal growth-associated protein that is highly expressed in the lateral nucleus of the amygdala and related thalamic and cortical structures (Shumyatsky et al, 2002). Rin showed low expression at the postnatal mouse brain, suggesting Rin may be dispensable for early brain but implicated Rin in mature neurons (Dhaka et al, 2003).
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