Myung Sook Oh

Bio: Myung Sook Oh is an academic researcher from Kyung Hee University. The author has contributed to research in topics: Neuroprotection & Dopaminergic. The author has an hindex of 35, co-authored 167 publications receiving 4084 citations.

Neuroprotective Effect of Ghrelin in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson’s Disease by Blocking Microglial Activation

Abstract: Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a (GHS-R1a) and is produced and released mainly from the stomach. It was recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of Parkinson’s disease (PD) neurodegeneration. However, the role of microglia in the neuroprotective properties of ghrelin is still unknown. Here we show that, in the mouse MPTP PD model generated by an acute regimen of MPTP administration, systemic administration of ghrelin significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers through the activation of GHS-R1a. We also found that ghrelin reduced nitrotyrosine levels and improved the impairment of rota-rod performance. Ghrelin prevents MPTP-induced microglial activation in the SNpc and striatum, the expression of pro-inflammatory molecules tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), and the activation of inducible nitric oxide synthase. The inhibitory effect of ghrelin on the activation of microglia appears to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial cells. Finally, in vitro administration of ghrelin prevented 1-methyl-4-phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, microglial activation, and the subsequent release of TNF-α, IL-1β, and nitrite in mesencephalic cultures. Our data indicate that ghrelin may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that ghrelin may be a valuable therapeutic agent for neurodegenerative diseases such as PD.

Mulberry fruit protects dopaminergic neurons in toxin-induced Parkinson's disease models

Abstract: Parkinson's disease (PD), one of the most common neurodegenerative disorders, is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) to the striatum (ST), and involves oxidative stress. Mulberry fruit from Morus alba L. (Moraceae) is commonly eaten, and has long been used in traditional oriental medicine. It contains well-known antioxidant agents such as anthocyanins. The present study examined the protective effects of 70 % ethanol extract of mulberry fruit (ME) against neurotoxicity in in vitro and in vivo PD models. In SH-SY5Y cells stressed with 6-hydroxydopamine (6-OHDA), ME significantly protected the cells from neurotoxicity in a dose-dependent manner. Other assays demonstrated that the protective effect of ME was mediated by its antioxidant and anti-apoptotic effects, regulating reactive oxygen species and NO generation, Bcl-2 and Bax proteins, mitochondrial membrane depolarisation and caspase-3 activation. In mesencephalic primary cells stressed with 6-OHDA or 1-methyl-4-phenylpyridinium (MPP+), pre-treatment with ME also protected dopamine neurons, showing a wide range of effective concentrations in MPP+-induced toxicity. In the sub-acute mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), ME showed a preventative effect against PD-like symptoms (bradykinesia) in the behavioural test and prevented MPTP-induced dopaminergic neuronal damage in an immunocytochemical analysis of the SNpc and ST. These results indicate that ME has neuroprotective effects in in vitro and in vivo PD models, and that it may be useful in preventing or treating PD.

Ghrelin ameliorates cognitive dysfunction and neurodegeneration in intrahippocampal amyloid-β1-42 oligomer-injected mice.

Abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and loss of neurons. Recently, it has been shown that ghrelin, a 28 amino acid peptide hormone produced from the stomach and hypothalamus, has been reported as a potential therapeutic agent for several neurological disorders, including Parkinson's disease (PD), stroke, epilepsy, multiple sclerosis, and spinal cord injury. Here we determined the effects of ghrelin on memory impairments and neuropathological changes in an AD mouse model induced by intrahippocampal injection of amyloid-β oligomers (AβO). We report that ghrelin: 1) rescues memory deficits in mice injected with AβO in the hippocampus; 2) decreases AβO-induced microgliosis in hippocampus; 3) attenuates hippocampal neuronal loss mediated by AβO; 4) prevents AβO-associated synaptic degeneration including cholinergic fiber loss. Taken together, our findings demonstrate that ghrelin can ameliorate AβO-induced cognitive impairment associated with neuroinflammation and neuronal loss. These results suggest that ghrelin may be a promising therapeutic agent for the treatment of AD.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The gut microbiota-brain axis in behaviour and brain disorders.

Abstract: In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health. In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.

Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis

Abstract: Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions.