Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner.

BACKGROUND: The risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD. METHODS: Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS. RESULTS: We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure. CONCLUSION: Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.

S.P.I.C. pedagogical simulator for gynecologic laparoscopy.

Laparoscopic surgery has numerous advantages, but this technique is difficult and requires specific training. This paper presents a simulator for gynecologic laparoscopic surgery called S.P.I.C. (Pedagogical Simulator for Gynecologic Laparoscopic Surgery), specifically designed for teaching. It includes a rail with 3 trocars already in place, and a computer monitor. Training using the simulator is divided into tasks and steps in order of increasing difficulty. Each step consists of training exercises and evaluations. Learning with the simulator is guided by software that allows instructors to personalize their lessons. This prototype has allowed us to put into place training for spatial localization and manipulation of surgical instruments in the abdominal cavity. An evaluation at a clinical site has allowed us to determine the improvements to be made on this prototype. Training with a simulator is part of a resident's regular curriculum and is not meant to replace on site hospital experience. Some imperfections in imaging still exist, due to inevitable technical limitations. Our initial choice was to emphasize realism and "real time", rather than the "aesthetic quality" of the images. Furthermore, by limiting our graphic expectations, we have been able to create a simulator at a reasonable overall price. The S.P.I.C. training tool remains experimental and is still in the process of being developed.