Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice

Background Alteration of immune status in the central nervous system (CNS) has been implicated in the development of post-traumatic stress disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear. Methods We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open-field test, and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single-cell mass cytometry. Microglia number and morphological changes in the hippocampus, prefrontal cortex, and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shocks exposure was performed to study the role of microglia in PTSD development and progress. Results We found microglia are the major brain immune cells that respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of the PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear. Conclusion Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

Microglial Deletion and Inhibition Alleviate Behavior of Post-Traumatic Stress Disorder in Mice

Background: Alteration of immune status in the central nervous system (CNS) has been implicated in the development of Post-Traumatic Stress Disorder (PTSD). However, the nature of overall changes in brain immunocyte landscape in PTSD condition remains unclear. Methods: We constructed a mouse PTSD model by electric foot-shocks followed by contextual reminders and verified the PTSD-related symptoms by behavior test (including contextual freezing test, open filed test and elevated plus maze test). We examined the immunocyte panorama in the brains of the naïve or PTSD mice by using single cell mass cytometry. Microglia number and morphological changes in hippocampus, prefrontal cortex and amygdala were analyzed by histopathological methods. The gene expression changes of those microglia were detected by quantitative real-time PCR. Genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure were performed to study the role of microglia in the PTSD development and progress. Results: We found microglia are the major brain immune cells respond to PTSD. The number of microglia and ratio of microglia to immunocytes was significantly increased on the fifth day of foot-shock exposure. Furthermore, morphological analysis and gene expression profiling revealed temporal patterns of microglial activation in the hippocampus of PTSD brains. Importantly, we found that genetic/pharmacological depletion of microglia or minocycline treatment before foot-shock exposure alleviated PTSD-associated anxiety and contextual fear. Conclusion: Our results demonstrated a critical role for microglial activation in PTSD development and a potential therapeutic strategy for the clinical treatment of PTSD in the form of microglial inhibition.

A REVIEW OF THE POSSIBLE CONSEQUENCES OF AN ELECTRICAL SHOCK ON THE BODY AND ITS MEDICOLEGAL ASPECTS

The electric current has always been a source of danger to man. The use of electricity in the home, office and factory has increased to such a tremendous extent that energized wires now form dangerous network at every turn. An electric shock occurs when a person comes in to contact with an electrical energy source. An electrical energy flows through a portion of the body causing a shock. Exposure to electrical energy may result in no injury at all or may result in devastating damage or death. In the present study compilation of electric current and its medicolegal aspects.

Foot shock stress generates persistent widespread hypersensitivity and anhedonic behavior in an anxiety-prone strain of mice

A significant subset of patients with urologic chronic pelvic pain syndrome (UCPPS) suffer from widespread, as well as pelvic, pain and experience mood-related disorders, including anxiety, depression, and panic disorder. Stress is a commonly-reported trigger for symptom onset and exacerbation within these patients. The link between stress and pain is thought to arise, in part, from the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the response to stress and can influence the perception of pain. Previous studies have shown that stress exposure in anxiety-prone rats can induce both pelvic and widespread hypersensitivity. Here, we exposed female A/J mice, an anxiety-prone inbred murine strain, to 10 days of foot shock stress to determine stress-induced effects on sensitivity, anhedonia, and HPA axis regulation and output in. At 1- and 28-days post-foot shock, A/J mice displayed significantly increased bladder sensitivity and hind paw mechanical allodynia. They also displayed anhedonic behavior, measured as reduced nest building scores and a decrease in sucrose preference during the 10-day foot shock exposure. Serum corticosterone was significantly increased at 1-day post-foot shock and bladder mast cell degranulation rates were similarly high in both sham- and shock-exposed mice. Bladder cytokine and growth factor mRNA levels indicated a persistent shift toward a pro-inflammatory environment following foot shock exposure. Together, these data suggest that chronic stress exposure in an anxiety-prone mouse strain may provide a useful translational model for understanding mechanisms that contribute to widespreadness of pain and increased comorbidity in a subset of UCPPS patients.