Biology subjects

Okun, M. S.

Publications and source records attributed to Okun, M. S..

2 recordsLinked to original sources

bioRxiv2024

A comparative analysis of Parkinson's disease and inflammatory bowel disease gut microbiomes highlights shared depletions in key butyrate-producing bacteria

Epidemiological studies reveal that a diagnosis of inflammatory bowel disease (IBD) is associated with an increased risk of developing Parkinsons disease (PD). The presence of gut dysbiosis has been documented in both PD and IBD patients, however it is currently unknown how alterations in the gut microbiome may contribute to the epidemiological link between both diseases. To identify shared and distinct features of the PD and IBD microbiome, we performed the first joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida, and directly compared the gut microbiomes from PD and IBD persons. Larger, publicly available PD and IBD metagenomic datasets were also analyzed to validate and extend our findings. Depletions in short-chain fatty acid (SCFA) producing bacteria, including Roseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium rectale, as well as depletions in SCFA synthesis pathways, were demonstrated across PD and IBD datasets. We posit that direct comparison of PD and IBD gut microbiomes will be important in identifying features within the IBD gut which may be associated with PD. The data revealed a consistent depletion in SCFA-producing bacteria across both PD and IBD, suggesting that loss of these microbes may influence the pathophysiology of both disease states.

neuroscience↗

bioRxiv2021

Functional characterization of the biogenic amine transporter system on human macrophages

Monocyte-derived macrophages are key players in tissue homeostasis and disease regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but the mechanisms governing biogenic amine signaling on and around immune cells remains nebulous. In the central nervous system, biogenic amine transporters are regarded as the master regulators of neurotransmitter signaling. While we and others have shown macrophages express these transporters, relatively little is known of their function on these cells. To address these knowledge gaps, we interrogated the function of norepinephrine (NET) and dopamine (DAT) transporters on human monocyte-derived macrophages. We found that both NET and DAT are present and can uptake substrate from the extracellular space at baseline. Not only was DAT expressed in cultured macrophages, but it was also detected in a subset of intestinal macrophages in situ. Surprisingly, we discovered a NET-independent, DAT-mediated immuno-modulatory mechanism in response to lipopolysaccharide (LPS). LPS induced reverse transport of dopamine through DAT, engaging autocrine/paracrine signaling loop that regulated the macrophage response. Removing this signaling loop enhanced the pro-inflammatory response to LPS. Finally, we found that this DAT-immune axis was disrupted in disease. Collectively, our data introduce a novel role for DAT in the regulation of innate immunity during health and disease.

neuroscience↗