Assessment of MALDI matrices for the detection and visualization of phosphatidylinositols and phosphoinositides in mouse kidneys through matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI).

Phosphatidylinositols and their phosphorylated derivatives, known as phosphoinositides, are crucial in cellular processes, with their abnormalities linked to various diseases. Thus, identifying and measuring phosphoinositide levels in tissues are crucial for understanding their contributions to cellular processes and disease development. One powerful technique for mapping the spatial distribution of molecules in biological samples is matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). This technique allows for the simultaneous detection and analysis of multiple lipid classes in situ, making it invaluable for unbiased lipidomic studies. However, detecting phosphoinositides with MALDI-MSI is challenging due to their relatively low abundance in tissues and complex matrix effects. Addressing this, our study focused on optimizing matrix selection and thickness for better detection of phosphatidylinositols and their phosphorylated forms in mouse kidney tissues. Various matrices were assessed, including 9AA, DAN, CMBT, and DHA, adjusting their coating to improve ionization efficiency. Our results demonstrate that DAN, DHA, and CMBT matrices produced high-intensity chemical images of phosphatidylinositol distributions within kidney sections. These matrices, particularly DAN, DHA, and CMBT, allowed the identification of even low-abundance phosphoinositides, through tentative identifications. Notably, DAN and DHA served as optimal candidates due to their prominent detection and ability to map a majority of phosphatidylinositol species, while CMBT showed potential detection capability for phosphatidylinositol triphosphate compounds. These findings not only provide valuable insights for future research on the involvement of phosphoinositides in kidney pathophysiology, but also propose the use of the identified optimal matrices, particularly DAN and DHA, as the preferred choices for enhanced detection and mapping of these lipid species in future studies.

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study).

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance. Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group-patients with current MDD (n = 20), (ii) remitted depressed group-patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups. Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice. Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=1.