Neuroprotective effects of MHY908, a PPAR α/γ dual agonist, in a MPTP-induced Parkinson’s disease model

Lee, Yujeong,Cho, Jung-Hyun,Lee, Seulah,Lee, Wonjong,Chang, Seung-Cheol,Chung, Hae Young,Moon, Hyung Ryong,Lee, Jaewon Elsevier 2019 Brain Research Vol.1704 No.-

<P><B>Abstract</B></P> <P>Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are considered promising therapeutic targets in several neurodegenerative diseases. A number of PPAR agonists have been shown to have neuroprotective properties in the presence of oxidative stress, neuroinflammatory response, and apoptosis in various neurodegenerative disease. MHY908 is a novel PPAR α/γ dual agonist, which has been shown to suppress inflammatory response and attenuate insulin resistance in aged rats and db/db mice. Here, we evaluated the neuroprotective effects of MHY908 in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pretreatment with MHY908 attenuated MPTP-induced dopaminergic neuronal loss and motor deficit. MPTP-induced glial activations were mitigated by MHY908 in the nigrostriatal pathway, and MHY908 effectively blocked 1-methyl-4-phenylpyridinium (MPP<SUP>+</SUP>)-induced cell death and ROS production in SH-SY5Y neuroblastoma cells. Further study revealed MHY908 inhibited MPP<SUP>+</SUP>-induced astroglial activation by suppressing NF-κB signaling in primary astrocytes. Taken together, the present study suggests that PPAR α/γ dual agonists be considered potentially useful preventions for PD and other neurodegenerative diseases associated with neuroinflammation.</P> <P><B>Highlight</B></P> <P> <UL> <LI> MHY908 attenuated MPTP-induced motor deficits and dopaminergic neuronal death. </LI> <LI> MHY908 also ameliorated MPTP-induced glial activation in the STR and SN. </LI> <LI> MHY908 pretreatment protected SH-SY5Y neuroblastoma cells against MPP<SUP>+</SUP> toxicity. </LI> <LI> Pretreatment of MHY908 inhibited MPP<SUP>+</SUP>-induced ROS generation. </LI> <LI> MHY908 treatment attenuated MPP<SUP>+</SUP>-induced primary astrocyte activation and nuclear translocation of NF-κB. </LI> </UL> </P>

Low-dose curcumin enhances hippocampal neurogenesis and memory retention in young mice

Yujeong Lee,Hee Ra Park,Joo Yeon Lee,Jaehoon Kim,Seonguk Yang,Chany Lee,Kipom Kim,Hyung Sik Kim,Seung-Cheol Chang,Jaewon Lee 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.5

Adult neurogenesis generates new functional neurons from adult neural stem cells in various regions, including the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of hippocampal dentate gyrus (DG). Available evidence shows hippocampal neurogenesis can be negatively or positively regulated by dietary components. In a previous study, we reported that curcumin (diferuloylmethane; a polyphenolic found in curry spice) stimulates the proliferation of embryonic neural stem cells (NSCs) by activating adaptive cellular stress responses. Here, we investigated whether subchronic administration of curcumin (once daily at 0.4, 2, or 10 mg/kg for 14 days) promotes hippocampal neurogenesis and neurocognitive function in young (5-week-old) mice. Oral administration of low-dose curcumin (0.4 mg/kg) increased the proliferation and survival of newly generated cells in hippocampus, but surprisingly, high-dose curcumin (10 mg/kg) did not effectively upregulate the proliferation or survival of newborn cells. Furthermore, hippocampal BDNF levels and phosphorylated CREB activity were elevated in only low-dose curcumin-treated mice. Passive avoidance testing revealed that low-dose curcumin increased cross-over latency times, indicating enhanced memory retention, and an in vitro study showed that low-concentration curcumin increased the proliferative activity of neural progenitor cells (NPCs) by upregulating NF1X levels. Collectively, our findings suggest that low-dose curcumin has neurogenic effects and that it may prevent age and neurodegenerative disease-related cognitive deficits.

Learning, memory deficits, and impaired neuronal maturation attributed to acrylamide

Lee, Seulah,Park, Hee Ra,Lee, Joo Yeon,Cho, Jung-Hyun,Song, Hye Min,Kim, Ah Hyun,Lee, Wonjong,Lee, Yujeong,Chang, Seung-Cheol,Kim, Hyung Sik,Lee, Jaewon TAYLOR & FRANCIS 2018 JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH PAR Vol.81 No.9

<P>Acrylamide (ACR) is a neurotoxin known to produce neurotoxicity characterized by ataxia, skeletal muscle weakness, cognitive impairment, and numbness of the extremities. Previously, investigators reported that high-dose (50mg/kg) ACR impaired hippocampal neurogenesis and increased neural progenitor cell death; however, the influence of subchronic environmentally relevant low dose-(2, 20, or 200g/kg) ACRs have not been examined in adult neurogenesis or cognitive function in mice. Accordingly, the aim of the present study was to investigate whether low-dose ACR adversely affected mouse hippocampal neurogenesis and neurocognitive functions. Male C57BL/6 mice were orally administered vehicle or ACR at 2, 20, or 200g/kg/day for 4weeks. ACR did not significantly alter the number of newly generated cells or produce neuroinflammation or neuronal loss in hippocampi. However, behavioral studies revealed that 200g/kg ACR produced learning and memory impairment. Furthermore, incubation of ACR with primary cultured neurons during the developmental stage was found to delay neuronal maturation without affecting cell viability indicating the presence of developmental neurotoxicity. These findings indicate that although exposure to in vivo low-dose ACR daily for 4weeks exerted no apparent marked effect on hippocampal neurogenesis, in vitro observations in primary cultured neurons noted adverse effects on learning and memory impairment suggestive of neurotoxic actions.</P>

Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson’s disease

Lee, Yujeong,Heo, Gwangbeom,Lee, Kyung Moon,Kim, Ah Hyun,Chung, Ki Wung,Im, Eunok,Chung, Hae Young,Lee, Jaewon Elsevier/North Holland 2017 Brain research Vol.1663 No.-

<P><B>Abstract</B></P> <P>Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson’s disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5mg/kg) for 12 consecutive days, and then on day 13, MPTP (20mg/kg, i.p.) was administered four times (with 2h intervals between injections) to induce PD. It was found that MPTP-induced motor dysfunction was ameliorated in the DNP-treated mice versus vehicle-treated controls. Additionally, DNP effectively attenuated dopaminergic neuronal loss observed in MPTP treated mice. Moreover, in primary cultured neurons, DNP at 10μM, but not at 100μM, prevented MPP<SUP>+</SUP>-induced cell death and mitochondrial membrane potential (MMP) reduction. In addition, DNP was observed to cause the nuclear translocation of Nrf2 in primary neurons. Taken together, these findings of the present study suggest that DNP protects dopaminergic neurons against neurodegeneration and maintains MMP integrity in PD by activating adaptive stress responses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> DNP attenuates MPTP-induced motor dysfunction and dopaminergic neuronal death. </LI> <LI> DNP pretreatment protects primary neurons against MPP<SUP>+</SUP>-induced cell death. </LI> <LI> Neuroprotective effects of DNP involve stabilization of MMP and adaptive stress response via Nrf2 activation. </LI> </UL> </P>

Association between Workplace Bullying and Burnout, Professional Quality of Life, and Turnover Intention among Clinical Nurses

Yujeong Kim,Eunmi Lee,Haeyoung Lee 한국간호과학회 2019 한국간호과학회 학술대회 Vol.2019 No.10

A Study on Factors Affecting Work Ability in Korean Workers

Yujeong Lee,Seong Rok Chang 대한인간공학회 2015 大韓人間工學會誌 Vol.34 No.4

Objective: The purpose of this study was to evaluate Korean workers" work ability and to identify its contributing factors. Background: In order for Korea to overcome the phenomena of becoming an aged society, older adults must participate in the workforce to balance out the population; workers" work ability must also be maintained. In addition, influential factors in employees" capabilities and degrees of importance thereof should be identified in advance to maintain work ability. Method: The Work Ability Index (WAI) questionnaire was completed by 5,708 Korean workers. Survey questionnaire consisted items of current work ability, physical and mental demands of the job, numbers of diseases, work impairment due to diseases, sick leaves, work ability in 2 years and mental resources. Results: Results indicated that work ability and length of service increased with age. It was also found that employees in administrative positions had greater work ability than site workers, workers directly managed by a supervisor had greater work ability than workers in cooperative firms, and workers who performed intellectual tasks had greater work ability than workers who performed physical labor. Job stress was additionally observed to contribute towards overall work ability. And musculoskeletal disorders (MSDs) were found to negatively affect work ability. Conclusion: The strongest determining factors in the work ability of Korean workers were stress level and mental state. Therefore, when the WAI is used to assess Korean workers, the weighting of WAI items pertaining to physical and mental abilities should be adjusted accordingly to account for these factors. Application: The result is expected to suggest that workers maintain work ability in an aged society.

Assessment of Work Ability of Korean Workers in the Shipbuilding Industry using FIOH Questionnaire

Yujeong Lee,Seong Rok Chang 대한인간공학회 2012 大韓人間工學會誌 Vol.31 No.1

Objective: The goal of this study was to assess work ability of Korean workers in the shipbuilding industry. Background: Old age is associated with inevitable time-dependent losses in physical capabilities. However the maintenance of physical capabilities is essential for continuing independence in old age. The work ability index(WAI) was constructed to reveal how well a worker is able to perform his or her work. Method: The WAI is a kind of survey methods developed to estimate the work capacity of aged workers by the Finish Institute of Occupational Health(FIOH) in 1998. The difference of the WAI between groups in each category was tested using the Kruskal-Wallis test, and the relationship between the WAI and the workers’ ages was tested by the Correlation test. Results: This study surveyed 2,709 persons working in the shipbuilding industry in Korea. The average WAI score for all workers was 40.0 denoting a Good Level. Also, workers in the shipbuilding industry had lower work ability, as compared to the results of other industries. The WAI was analyzed for different age groups(≤29; 30~34; 35~39; 40~44; 45~49; 50~54; ≥55). The results of Kruskal-Wallis test showed that significant difference was identified on the effect of aging(p<0.05). Conclusion: Advanced countries like the Finland showed decreasing tendency in good and excellent levels as aged, but there was no decreasing tendency in Korean population. The results may be attributable to the general characteristics of Korean society, such as poor social security and burden caused by role of the patriarch. It may bring forth higher work ability in aged population even their physical condition is getting worse. Application: This finding could be used for developing more accurate assessment tool of work ability for working environment.

Approaches to Stretchable Polymer Active Channels for Deformable Transistors

Lee, Yujeong,Shin, Minkwan,Thiyagarajan, Kaliannan,Jeong, Unyong American Chemical Society 2016 Macromolecules Vol.49 No.2

<P>The fabrication of deformable devices has been explored by interconnecting nonstretchable unit devices with stretchable conductors or by developing stretchable unit devices consisting of all stretchable device components such as electrodes, active channels, and dielectric layers. Most researches have followed the first approach so far, and the researches based on the second approach are at the very beginning stage. This paper discusses the perspectives of the second approach, specifically focusing on the polymer semiconductor channel layers, that is expected to facilitate high density device integration in addition to large area devices including polymer solar cells and light-emitting diodes. Three different routes are suggested as separate sections according to the principles imparting stretchability to polymer semiconductor layers: structural configurations of rigid semiconductors, two-dimensional network structure of semiconductors on elastomer substrates, and ductility enhancement of semiconductor films. Each section includes two subsections divided by the methodological difference. This Perspective ends with discussion on the future works for the routes and the challenges related to other device components.</P>

Ongoing endeavors to detect mobilization of transposable elements

Yujeong Lee,Una Ha,Sungjin Moon 생화학분자생물학회 2022 BMB Reports Vol.55 No.7

Transposable elements (TEs) are DNA sequences capable ofmobilization from one location to another in the genome. Sincethe discovery of ‘Dissociation (Dc) locus’ by Barbara McClintockin maize (1), mounting evidence in the era of genomics indicatesthat a significant fraction of most eukaryotic genomes is composedof TE sequences, involving in various aspects of biologicalprocesses such as development, physiology, diseasesand evolution. Although technical advances in genomics havediscovered numerous functional impacts of TE across species,our understanding of TEs is still ongoing process due to challengesresulted from complexity and abundance of TEs in thegenome. In this mini-review, we briefly summarize biology ofTEs and their impacts on the host genome, emphasizing importanceof understanding TE landscape in the genome. Then,we introduce recent endeavors especially in vivo retrotranspositionassays and long read sequencing technology for identifyingde novo insertions/TE polymorphism, which will broaden ourknowledge of extraordinary relationship between genomic cohabitantsand their host.

Dense Matter at RAON: Challenges and Possibilities

Yujeong Lee,Chang-Hwan Lee,T. Gaitanos,Youngman Kim 한국물리학회 2016 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.69 No.9

Dense nuclear matter is ubiquitous in modern nuclear physics because it is related to many interesting microscopic and macroscopic phenomena such as heavy ion collisions, nuclear structure, and neutron stars. The on-going rare isotope science project in Korea will build up a rare isotope accelerator complex called RAON. One of the main goals of RAON is to investigate rare isotope physics including dense nuclear matter. Using the relativistic Boltzmann-Uehling-Uhlenbeck (RBUU) transport code, we estimate the properties of nuclear matter that can be created from low-energy heavyion collisions at RAON.We give predictions for the maximum baryon density, the isospin asymmetry and the temperature of nuclear matter that would be formed during 197Au+197Au and 132Sn+64Ni reactions. With a large isospin asymmetry, various theoretical studies indicate that the critical densities or temperatures of phase transitions to exotic states decrease. Because a large isospin asymmetry is expected in the dense matter created at RAON, we discuss possibilities of observing exotic states of dense nuclear matter at RAON for large isospin asymmetry.