Biology subjects

Oh, J.-Y.

Publications and source records attributed to Oh, J.-Y..

4 recordsLinked to original sources

bioRxiv2023

Discrete projections from MCH neurons mediate anti-parkinsonian effects of acupuncture

Parkinsons disease (PD) presents with typical motor dysfunction and non-motor symptoms, including memory loss. Although acupuncture is suggested as an alternative therapy for PD, its neuroanatomical mechanisms remain unclear. We demonstrate that acupuncture ameliorates both motor and memory deficits in PD mice through activation of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus and zona incerta (LH/ZI)--MCHLH/ZI-- via nerve conduction. We identify two distinct subpopulations of MCHLH/ZI projecting to the substantia nigra and hippocampus, each of which is responsible for controlling motor and memory function. This effect can be attributed to MCH-mediated recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, MCHLH/ZI constitutes not only the neuroanatomical basis of acupuncture but also a potential cellular target for treating both motor and non-motor PD symptoms. One-Sentence SummaryAcupuncture alleviates both motor and non-motor symptoms in Parkinsons disease by activating two distinct MCH projections.

neuroscience↗

bioRxiv2023

Ampk activation by glycogen expenditure primes the exit of naive pluripotency

Embryonic and epiblast stem cells in pre-and post-implantation embryos are characterized by their naive and primed states, respectively, which represent distinct phases of pluripotency. Thus, the cellular transition from naive to primed pluripotency recapitulates a drastic metabolic and cellular remodeling after implantation to adapt to changes in extracellular conditions. Here, we found that inhibition of Ampk occurred during naive transition with two conventional inhibitors (2i) of the Mek1 and Gsk3{beta} pathways. The accumulation of glycogen due to the inhibition of Gsk3{beta} was responsible for Ampk inhibition, which accounted for high de novo fatty acid synthesis in naive embryonic stem cells (ESCs). The knockout of glycogen synthase 1 (Gys1) in naive ESCs (GKO), resulting in a drastic glycogen loss, led to a robust Ampk activation and lowered the level of fatty acids. GKO lost the cellular characteristics of naive ESCs and rapidly transitioned to a primed state, as evidenced by a decrease in pluripotency markers in teratoma from GKO. The characteristics of GKO were restored by the simultaneous knockout of Ampk. These findings suggest that glycogen in naive ESCs within the blastocyst may act as a signaling molecule for the timely activation of Ampk, thus ultimately contributing to the transition to the epiblast stage. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/541467v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@118ea81org.highwire.dtl.DTLVardef@cbe4bforg.highwire.dtl.DTLVardef@16d5c1org.highwire.dtl.DTLVardef@12b825c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming process that leads to the emergence of injury-responsive cells with fetal-like characteristics in the intestinal epithelium. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells through forced partial reprogramming in vivo using "Yamanaka factors" (Oct4, Sox2, Klf4, and c-Myc: OSKM). The OSKM-induced dedifferentiation showed similar molecular features of intestinal regeneration, including a rapid transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing a gene signature of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following ionizing radiation-induced acute tissue damage. In contrast to normal intestinal regeneration, which involves epi-mesenchymal crosstalk through induction of Ptgs2 (encoding Cox2) upon injury, the OSKM expression promotes the autonomous production of prostaglandin E2 via epithelial Ptgs1 (encoding Cox1) expression. These results indicate that prostaglandin synthesis is a common mechanism for intestine epithelial regeneration but involves a different enzyme (Ptgs1 for Cox1) when partial reprogramming is directly applied to the intestinal epithelium.

cell biology↗

bioRxiv2019

Phosgene Inhalation Causes Hemolysis and Acute Lung Injury

Phosgene (Carbonyl Chloride, COCl2) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis of solvents (degreasers, cleaners). It is a sweet smelling gas, and therefore does not prompt escape by the victim upon exposure. Supplemental oxygen and ventilation are the only available management strategies. This study was aimed to delineate the pathogenesis and identify novel biomarkers of acute lung injury post exposure to COCl2 gas. Adult male and female C57BL/6 mice (20-25 g), exposed to COCl2 gas (10 or 20ppm) for 10 minutes in environmental chambers, had a dose dependent reduction in PaO2 and an increase in PaCO2, 1 day post exposure. However, mortality increased only in mice exposed to 20ppm of COCl2 for 10 minutes. Correspondingly, these mice (20ppm) also had severe acute lung injury as indicated by an increase in lung wet to dry weight ratio, extravasation of plasma proteins and neutrophils into the bronchoalveolar lavage fluid, and an increase in total lung resistance. The increase in acute lung injury parameters in COCl2 (20ppm, 10min) exposed mice correlated with simultaneous increase in oxidation of red blood cells (RBC) membrane, RBC fragility, and plasma levels of cell-free heme. In addition, these mice had decreased plasmalogen (plasmenylethanolamine) and elevated levels of their breakdown product, polyunsaturated lysophosphatidylethanolamine, in the circulation suggesting damage to cellular plasma membranes. This study highlights the importance of free heme in the pathogenesis of COCl2 lung injury and identifies plasma membrane breakdown product as potential biomarkers of COCl2 toxicity.

physiology↗