Biology subjects

Oh, M. S.

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

3 recordsLinked to original sources

bioRxiv2023

Methylglyoxal is the main culprit to impairing neuronal function: mediated through tryptophan depletion.

Depression is a common and prevalent illness and the exact cause of major depressive disorder is not known. Here, we investigated how methylglyoxal (MGO) stress induces depression and unveiled the potential molecular mechanism. Our in vivo results suggested that MGO caused depression in mice, confirmed by several behavioral tests. Interestingly, it halted the mices brains tryptophan levels and its related neurotransmitters. In addition, MGO induced a reduction in the number of cells in different hippocampal regions. Moreover, it decreased tryptophan hydroxylase 1 (TPH1) and tryptophan hydroxylase 1 (TPH2) levels in the brain and large intestine. Surprisingly, MGO showed the highest affinity and trapping ability toward tryptophan. Most importantly, combined treatment with MGO-tryptophan displayed similar effects as those exhibited by the tryptophan-null treatment in neuronal cells, which included neuronal apoptosis, decrease TPH1 and TPH2 levels, and inhibition of neuronal outgrowth. However, tryptophan treatment improved MGO induced depression-like behavior of mice and recovered the loss of neuronal and hippocampal cells. Subsequently, it also induced MGO detoxifying factors, tryptophan levels, and reduces inflammation in the intestine. Collectively, our data revealed that MGO induced depression facilitated by neuronal and synaptic dysfunction is mediated through the disturbance of tryptophan metabolism in the brain and intestine.

neuroscience↗

bioRxiv2019

High-throughput 16S rRNA gene sequencing reveals gut microbial changes in 6-hydroxydopamine-induced Parkinsons disease mice

Recently, there has been a rapid increase in studies on the relationship between brain diseases and gut microbiota, and clinical evidence on gut microbial changes in Parkinsons disease (PD) has accumulated. 6-hydroxydopamine (6-OHDA) is a widely used neurotoxin that leads to PD pathogenesis, but whether the alterations of gut microbial community in 6-OHDA-treated mice has not been investigated. Here we performed the 16S rRNA gene sequencing to analyze changes in gut microbial community of mice. We found that there were no significant changes in species richness and its diversity in the 6-OHDA-lesioned mice. The relative abundance of Lactobacillus gasseri and L. reuteri probiotic species in feces of 6-OHDA-lesioned mice was significantly decreased compared with those of sham-operated mice, while the commensal bacterium Bacteroides acidifaciens in 6-OHDA-treated mice was remarkably higher than sham-operated mice. These results provides a baseline for understanding the microbial communities of 6-OHDA-induced PD model to investigate the role of gut microbiota in the pathogenesis of PD.

neuroscience↗

bioRxiv2018

A non-canonical JAGGED1 signal to JAK2 mediates osteoblast commitment in cranial neural crest cells

During craniofacial development, cranial neural crest (CNC) cells migrate into the developing face and form bone through intramembranous ossification. Loss of JAGGED1 (JAG1) signaling in the CNC cells is associated with maxillary hypoplasia or maxillary bone deficiency (MBD) in mice and recapitulates the MBD seen in humans with Alagille syndrome. JAGGED1, a membrane-bound NOTCH ligand, is required for normal craniofacial development, and Jagged1 mutations in humans are known to cause Alagille Syndrome, which is associated with cardiac, biliary, and bone phenotypes and these children experience increased bony fractures. Previously, we demonstrated deficient maxillary osteogenesis in Wnt1-cre;Jagged1f/f (Jag1CKO) mice by conditional deletion of Jagged1 in maxillary CNC cells. In this study, we investigated the JAG1 signaling pathways in a CNC cell line. Treatment with JAG1 induced osteoblast differentiation and maturation markers, Runx2 and Ocn, respectively, Alkaline Phosphatase (ALP) production, as well as classic NOTCH1 targets, Hes1 and Hey1. While JAG1-induced Hes1 and Hey1 expression levels were predictably decreased after DAPT (NOTCH inhibitor) treatment, JAG1-induced Runx2 and Ocn levels were surprisingly constant in the presence of DAPT, indicating that JAG1 effects in the CNC cells are independent of the canonical NOTCH pathway. JAG1 treatment of CNC cells increased Janus Kinase 2 (JAK2) phosphorylation, which was refractory to DAPT treatment, highlighting the importance of the non-canonical NOTCH pathway during CNC cells osteoblast commitment. Pharmacologic inhibition of JAK2 phosphorylation, with and without DAPT treatment, upon JAG1 induction reduced ALP production and, Runx2 and Ocn gene expression. Collectively, these data suggest that JAK2 is an essential component downstream of a non-canonical JAG1-NOTCH1 pathway through which JAG1 stimulates expression of osteoblast-specific gene targets in CNC cells that contribute to osteoblast differentiation and bone mineralization.

molecular biology↗