Change of Rin1 and Stathmin in the Animal Model of Traumatic Stresses

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.

Effects of Stathmin 1 Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress

“…SDS induced no significant difference in total STMN1 expression among the four brain regions in the control, unsusceptible, and susceptible groups of WT mice. STMN1 expression in the AMY and HIP reportedly decreased after a single prolonged stress treatment and immobilization stress in rats [40]. In contrast, pS16- STMN1 expression levels significantly decreased in the PFC of unsusceptible and susceptible groups of WT mice compared to the control group.…”

Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala

“…Strongly involved in forming emotional memories, especially fear-related memories, the amygdala is thus regarded as the central brain region and attracts many scientists’ special attention. Using animal model of PTSD, previous studies have found that glucocorticoid receptor ( Kohda et al, 2007 ), 5-HT 2 C ( Harada et al, 2008 ), Rin1 and Stathmin ( Han et al, 2017 ), beta-adrenoreceptors ( Ronzoni et al, 2016 ), and beta-arrestin-2 ( Ding et al, 2017 ) are involved in the PTSD-associated behaviors. Besides, the amygdala is composed of several functionally distinct nuclei that interact during stress responses.…”

“…Exaggerated of the amygdala activity has been observed in response to trauma-related stimuli ( Shin et al, 1997 ; Liberzon et al, 1999 ; Pissiota et al, 2002 ; Hendler et al, 2003 ), and also during acquisition of conditioned fear ( Bremner et al, 2005 ). Using animal model of PTSD, a few studies found that 5-HT2C ( Harada et al, 2008 ), Rin1 and Stathmin ( Han et al, 2017 ), beta-adrenoreceptors ( Ronzoni et al, 2016 ), Neuropeptide S ( Cohen et al, 2018 ), and beta-arrestin-2 ( Ding et al, 2017 ) may be implicated in PTSD associated behaviors. Recently, through using c-Fos or other markers of neuronal activity, increased activation of the amygdala was found to be associated with traumatic stress-induced behavioral changes, such as anxiety-like behaviors and deficit in fear extinction ( Muigg et al, 2008 ; Hoffman et al, 2014 ; Ritov et al, 2014 ; Yu et al, 2015 ; Knox et al, 2018 ).…”

Combined brain‐derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post‐traumatic stress disorder

“…SPS mimics many aspects of the pathophysiological abnormalities associated with PTSD, and also some aspects of the behavioral characteristics. 20,21 For instance, SPS rats exhibit enhanced glucocorticoid negative feedback, 22 sleep abnormalities, 23 enhanced anxiety, [24][25][26] hyperarousal 27 and enhanced contextual freezing 28 as well as the expected therapeutic response to long-term treatment with paroxetine on enhanced fear memory. 29 Several studies have showed impaired fear extinction in SPS rats, 30,31 which is alleviated by repeated administration of D-cycloserine 32 or by single administration of vorinostat, a histone deacetylase inhibitor.…”