Biology subjects

Mason, H. D.

Publications and source records attributed to Mason, H. D..

3 recordsLinked to original sources

bioRxiv2024

CD300f immune receptor is a microglial tissue damage sensor and regulates efferocytosis after brain damage

Microglia, the resident phagocytes of the central nervous system (CNS), continuously monitor the parenchyma and surrounding borders and are the primary responders to brain damage. CD300f is a lipid-sensing immunoreceptor present in the microglial cell membrane, which binds to phosphatidylserine and other lipid mediators. Defining the functional microglial sensome is critical to understand their function and cell state determination. Using intravital two-photon microscopy we show that microglia lacking the CD300f receptor fail to detect environmental damage cues after a laser ablation injury. After a mild traumatic brain injury or after the intracortical injection of apoptotic cells, CD300f-/- microglia showed reduced capacity for detecting and phagocytosing dyeing cells, leading to the accumulation of dead cells in the neural parenchyma. Moreover, at later timepoints, increased accumulation of dyeing cells was found inside CD300f-/- microglia in vivo and in bone marrow-derived macrophages in vitro, suggesting that these cells display a reduced capacity for metabolizing phagocytosed cells. Finally, CD300f deficiency increased functional compromise after a contusive traumatic brain injury, associated to increased conservation of brain tissue. Collectively, these results suggest that CD300f function as a damage-associated molecular pattern (DAMP) receptor that coordinates microglial process reaction towards tissue debris and highlights its central role in microglial sensome machinery and in the modulation of in vivo microglial efferocytosis.

neuroscience↗

bioRxiv2023

Mechanism of action of Vitamin D (1,25-(OH)2-D3) on ovarian follicle growth: implications for women with Vitamin D deficiency and PCOS

Numerous observational and interventional studies have investigated the link between Vitamin D (VD) deficiency and reproductive outcomes, with contradictory results. VD is known to regulate steroidogenic enzymes crucial for human granulosa and cumulus cell function and genes that play a critical role in folliculogenesis have a vitamin D response element (VDRE) on their promoters. This study investigated whether deficient levels of 1,25-(OH)2-D3 altered ovarian cell function; and if the ovary could obtain bioactive 1,25-(OH)2-D3 via local enzymatic expression of CYP27B1, to counteract systemic deficiency. A variety of cells and tissues were used for the in vitro experiments as practicable. We have shown for the first time an increase in VDR expression in theca of larger compared to smaller follicles, which along with the ability of 1,25-(OH)2-D3 to decrease Anti-Mullerian hormone (AMH) expression, supports a role for 1,25-(OH)2-D3 in theca and granulosa cell function. Conversely, we have shown that very levels of 1,25-(OH)2-D3 equivalent to hypovitaminosis, inhibited thecal production of androstenedione and cAMP-driven E2 production. Human thecal and unluteinised GC are incredibly hard to obtain for research purposes, highlighting the uniqueness of our data set. For the first time we have demonstrated that deficient levels of 1,25-(OH)2-D3 also down-regulated insulin receptor expression, potentially reducing insulin sensitivity. We have shown that the ovary expresses CYP27B1 allowing it to make local bioactive 1,25-(OH)2-D3 which along with the upregulation in VDR expression in all ovarian cellular compartments, could be protective locally in counteracting systemic VD deficiency. To conclude a severely deficient VD environment (<2nM or <1ng/ml) could contribute to impaired ovarian cell function and hence potentially affect folliculogenesis/ovulation, but levels associated with mild deficiency may have less impact, apart from in the presence of hyperinsulinemia and insulin resistance.

physiology↗

bioRxiv2020

Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brains poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely post-sTBI, significantly enhanced cellular repair and gross motor function recovery when compared to controls, 20 weeks post-sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations, demonstrated the significant recovery of reach-to-grasp function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely post-sTBI can support complex cellular, vascular, and neuronal circuit repair, chronically after sTBI.

bioengineering↗