Antidepressant treatment effects on hippocampal protein turnover: Molecular and spatial insights from mass spectrometry.

A major challenge in managing depression is that antidepressant drugs take a long time to exert their therapeutic effects. For the development of faster-acting treatments, it is crucial to get an improved understanding of the molecular mechanisms underlying antidepressant mode of action. Here, we used a novel mass spectrometry-based workflow to investigate how antidepressant treatment affects brain protein turnover at single-cell and subcellular resolution. We combined stable isotope metabolic labeling, quantitative Tandem Mass Spectrometry (qTMS) and Multi-isotope Imaging Mass Spectrometry (MIMS) to simultaneously quantify and image protein synthesis and turnover in hippocampi of mice treated with the antidepressant paroxetine. We identified changes in turnover of individual hippocampal proteins that reveal altered metabolism-mitochondrial processes and report on subregion-specific turnover patterns upon paroxetine treatment. This workflow can be used to investigate brain protein turnover changes in vivo upon pharmacological interventions at a resolution and precision that has not been possible with other methods to date. Our results reveal acute paroxetine effects on brain protein turnover and shed light on antidepressant mode of action.

An in-vivo study of the safety of copper-containing intrauterine devices in 3.0 Tesla magnetic resonance imaging.

PURPOSE: The aim of this study is to prospectively evaluate whether women with copper-containing intrauterine devices (Cu-IUD), currently listed as MR conditional, can safely undergo 3.0 Tesla (3 T) magnetic resonance imaging (MRI). METHODS: 73 women, age 18-54 years old, with a Cu-IUD who were undergoing MRI for any reason were included consecutively. Pre- and post-MRI standard pelvic ultrasound examinations were completed to determine the appropriate pre- and post-MRI positioning of the Cu-IUD. Displaced IUDs were defined by IUD crossbars not in the fundal portion of the endometrial cavity, a visualized tip in the mid or lower uterus, any part of the device located in the cervical canal or outside of the endometrial canal, a fractured device, or a non-visualized IUD. Additionally, a questionnaire was completed by participants to determine the level of pre- and post-MRI pelvic pain. RESULTS: There were zero observed displaced Cu-IUDs on post-MRI pelvic ultrasounds (p = 0/70, 95% CI 0, .043). Three participants were dropped from the study due to malpositioned IUDs on pre-MRI pelvic ultrasound. Six patients reported new or worsening pelvic pain/discomfort during or after their MRI examination. CONCLUSION: Our results suggest that performing 3 T MRI using a low SAR setting does not cause displacement of Cu-IUDs, with zero out of 70 patients demonstrating IUD displacement.