scholarly journals Ablation of NPFFR2 in Mice Reduces Response to Single Prolonged Stress Model

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2479
Author(s):  
Ya-Tin Lin ◽  
Yi-Ling Huang ◽  
Sze-Chi Tsai ◽  
Jin-Chung Chen
Keyword(s):  
Hpa Axis ◽  
Clinical Symptoms ◽  
Physical Restraint ◽  
Mrna Levels ◽  
Stress Exposure ◽  
Post Traumatic Stress ◽  
Behavioral Correlates ◽  
Ether Anesthesia ◽  
Single Prolonged Stress ◽  
Prolonged Stress

Mental stress is highly related to many clinical symptoms and disorders, as it activates the hypothalamic-pituitary-adrenocortical (HPA) axis to affect a wide variety of physiological functions. Furthermore, stress leads to the aberrations in HPA axis activity and disruptions of body homeostasis. It was previously shown that neuropeptide FF (NPFF) regulates the HPA axis through the activation of hypothalamus paraventricular nucleus (PVN), and genetic overexpression or pharmacological stimulation of NPFF receptor 2 (NPFFR2) triggers hyperactivity of HPA axis and suppresses behavioral correlates of emotion in mice. In this study, we further examined the role of NPFFR2 in stress response in mice by utilizing a single prolonged stress (SPS). SPS is considered a model of post-traumatic stress disorder (PTSD), and mice undergo physical restraint, forced swimming, and ether anesthesia within a day followed by social isolation for one week. NPFFR2 knockout B6 mice were generated by CRISPR/Cas9 technology and exposed to SPS. The NPFFR2 knockouts showed resistance to stress exposure-induced anxiety-like behaviors and HPA axis hyperactivity. Additionally, the hippocampal mRNA levels of glucocorticoid receptor and mineralocorticoid receptor were reduced in wild-type (WT) mice but not in NPFFR2 knockouts after stress exposure. Our data also suggested that NPFFR2 knockout mice have stronger negative feedback on the HPA axis after exposure to SPS. Mice with intra-PVN Npffr2 shRNA injection displayed trends toward resistance to SPS exposure in both behavioral and molecular assays. Together, our findings suggest that NPFFR2 may be a potential therapeutic target for disorders relating to stress/anxiety and HPA dysregulation.

102 Single-Prolonged Stress as a Model of PTSD in Mice: Effects on Sleep and Anxiety

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A42-A42
Author(s):  
Katelyn Gutowsky ◽  
Carolyn Jones ◽  
Miranda Lim
Keyword(s):  
Rem Sleep ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Power Spectra ◽  
Post Traumatic Stress ◽  
Sleep State ◽  
Single Prolonged Stress ◽  
Post Traumatic ◽  
And Control ◽  
Prolonged Stress

Abstract Introduction Sleep problems are common in humans with post-traumatic stress disorder (PTSD). Rapid eye movement (REM) sleep is involved in processing emotional memories; it is often disrupted in those with PTSD, and may be related to increased anxiety. Single prolonged stress (SPS) is a protocol used to model PTSD in rats, however little is known about how this model impacts sleep in mice. Prior research suggests SPS produces short term disturbances in REM sleep and increases in anxiety-like behavior, but further validation of this model is needed to understand how SPS impacts sleep and anxiety-like behaviors in mice specifically, as they have greater potential for transgenic manipulation Methods C57BL6/J mice underwent a SPS protocol in which they were tube-restrained for 2 hours, followed by a 15 minute forced swim in a group, ether exposure until loss of consciousness, and 10 days of social isolation. Following SPS, mice were tested for anxiety-like behavior in a light-dark box and sleep was measured from surgically implanted EEG and EMG leads. Time spent in wake, REM sleep, and non-REM sleep was quantified for 24 continuous hours in SPS and Control mice. Results There were no significant effects of SPS on the amount of time spent in any vigilance state, or in sleep-wake transitions. However, SPS-exposed mice showed significantly more anxiety-like behavior. EEG power spectra were analyzed in relevant frequency bands during each sleep state, and exploratory analyses were conducted Conclusion Minimal effects on sleep macroarchitecture were seen in mice 10 days after SPS. It is possible that sleep disturbances seen immediately after trauma exposure (such as in prior studies in rats) may have diminished over time. Further studies will need to include additional timepoints and analysis of sleep microarchitecture following SPS, and in other mouse models of PTSD, in order to more comprehensively examine changes in sleep. Support (if any) VA CDA #IK2 BX002712, Portland VA Research Foundation, Medical Research Foundation

scholarly journals Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress

2016 ◽  
Vol 303 ◽  
pp. 228-237 ◽  
Author(s):  
Shane A. Perrine ◽  
Andrew L. Eagle ◽  
Sophie A. George ◽  
Kostika Mulo ◽  
Robert J. Kohler ◽  
...  
Keyword(s):  
Mouse Model ◽  
Stress Exposure ◽  
Single Prolonged Stress ◽  
Prolonged Stress

scholarly journals An Advanced Transcriptional Response to Corticosterone After Single Prolonged Stress in Male Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Jinlan Ding ◽  
Xinzhao Chen ◽  
Fang Han ◽  
Onno C. Meijer
Keyword(s):  
Negative Feedback ◽  
Target Genes ◽  
Dorsal Hippocampus ◽  
Rapid Change ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Post Traumatic Stress ◽  
Transcriptional Responses ◽  
Single Prolonged Stress ◽  
Prolonged Stress

Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes (t = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.

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