Biology subjects

Bringart, M.

Publications and source records attributed to Bringart, M..

3 recordsLinked to original sources

bioRxiv2025

Aerosolized ApoA1 Nanoparticles Synthesized by Microfluidics Cross the Lung Barrier and Modulate Inflammation

High-density lipoproteins exert vasculoprotective effects, mainly through apolipoprotein A1, which has led to the development of treatments based on apolipoprotein A1 nanoparticles (A1NPs) administered intravenously, mainly for the treatment of cardiovascular diseases. However, their potential as therapy for lung pathologies has not yet been explored. In this work, we produced A1NPs using microfluidics and characterized their therapeutic potential for lung delivery. Their morphology was characterized by dynamic light scattering and transmission electron microscopy. A1NPs toxicity and cellular uptake were performed on both endothelial (HMEC-1) and epithelial (A549) cells and their anti-inflammatory activity was evaluated on TNF--stimulated HMEC-1. A1NPs biodistribution was explored in lung mice after aerosolization and their transcytosis was further investigated using A549 air-liquid interface model. Our results demonstrate that the microfluidic synthesis of A1NPs was reproducible and yielded discoidal particles with sizes ranging from 7-12 nm. A1NPs were internalized by both cells without being cytotoxic and significantly reduced IL-6 expression. Aerosolization resulted in homogeneous distribution in lungs, without causing an immunogenic response. A fraction of A1NPs crossed alveolar epithelial cells both in vitro and in vivo, paving the way for future therapeutic strategies targeting not only the lungs, but also other peripheral organs. These results are promising for the use of A1NPs as vectors for therapeutic molecules, which could exert synergistic protective effects with Apolipoprotein A1. This is the first study to show the non-invasive administration of A1NPs by aerosolization, which may improve their bioavailability in lungs and appears to be a promising approach for treating lung diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/663869v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@2f3436org.highwire.dtl.DTLVardef@10cd3aeorg.highwire.dtl.DTLVardef@11d7542org.highwire.dtl.DTLVardef@fd627a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Alteration of nociceptive Schwann cells in a mouse model of peripheral neuropathy in prediabetic condition

Diabetic peripheral neuropathy (DPN) is characterized by progressive and symmetrical sensory abnormalities and constitutes one of the earliest and main complications of diabetes. DPN is characterized by heterogeneous sensory symptoms such as chronic pain, tingling, burning or loss of sensation. Nociceptive Schwann cells (nSCs), a recently identified subtypes of dermal Schwann cells support terminal nerve fibers in mouse skin and contribute to mechanical sensation and neuropathic pain. While terminal nerve fibers density is evaluated in DPN models, there is currently no data about nSCs number and integrity during the early stages of the disease. In the present study, we determined the quantitative differences in terminal nerve fiber density as well as nSCs number and cellular extensions between control and high-fat diet (HFD) induced diabetic mice presenting with a neuropathic phenotype. We also characterized L1CAM as a reliable and specific marker of nSCs, a cell type previously assessed by the expression of S100{beta} and Sox10. Interestingly, we observed a decrease in intraepidermal nerve fiber density (IENFD) associated with a significant reduction of nSCs in the glabrous foot skin of neuropathic mice. Overall, this study identifies L1CAM as a new marker of nSCs and indicates that these cells are impacted in diabetic peripheral neuropathy.

neuroscience↗

bioRxiv2024

PCSK9 deficiency promotes the development of peripheral neuropathy

PCSK9 best-known and studied function is to induce the hepatic degradation of the low-density lipoprotein receptor (LDLR), thereby increasing the concentration of LDL-cholesterol (LDL-C) in the blood. Beyond its effects on LDL, recent studies have reported pleiotropic effects of PCSK9 notably in septic shock, vascular inflammation, viral infection, and cancer. While the functional and structural integrity of peripheral nerves are critically influenced by circulating lipids, the impact of PCSK9 in the peripheral nervous system is unknown. In this study, we investigated the consequences of PCSK9 deficiency on peripheral nerves. We found that PCSK9 deletion in mice leads to peripheral neuropathy characterized by a reduction of thermal and mechanical pain sensations. PCSK9 deficient mice also presented skin structural changes with a reduction of number of terminal nociceptive Schwann cells, Remak fiber axonal swelling, as well as hypomyelination of small nerve fibers. Interestingly, peripheral nerves of PCSK9 deficient mice presented an upregulation of the fatty acid transporter CD36 expression which correlated with an increase in nerve lipid contents and structural mitochondrial abnormalities. Our findings demonstrate that PCSK9 plays a critical role in the peripheral nerves by regulating lipid homeostasis, and its deficiency could lead to the development of symptoms related to peripheral neuropathy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/583154v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1469ef8org.highwire.dtl.DTLVardef@16ebcd9org.highwire.dtl.DTLVardef@1305cbborg.highwire.dtl.DTLVardef@181758_HPS_FORMAT_FIGEXP M_FIG C_FIG PCSK9 modulates nerve energy metabolism and health. Created with BioRender.com.

neuroscience↗