Browsing by Author "Academia Sinica, Institute of Biomedical Sciences"

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    Enhanced contextual fear memory in peroxiredoxin 6 knockout mice is associated with hyperactivation of MAPK signaling pathway
    (2021-12-01) Sarayut Phasuk; Tanita Pairojana; Pavithra Suresh; Chee Hing Yang; Sittiruk Roytrakul; Shun Ping Huang; Chien Chang Chen; Narawut Pakaprot; Supin Chompoopong; Sutisa Nudmamud-Thanoi; Ingrid Y. Liu; Siriraj Hospital; Academia Sinica, Institute of Biomedical Sciences; Naresuan University; Tzu Chi University; Thailand National Center for Genetic Engineering and Biotechnology
    Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemic Prdx6 knockout (Prdx6−/−) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mouse Prdx6 into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTRK2, AKT, and phospho-ERK1/2, cPLA2 were significantly upregulated in the hippocampus of Prdx6−/− mice during the retrieval stage of contextual fear memory. The distribution of PRDX6 found in the astrocytes was also observed throughout the hippocampus. This study identifies PRDX6 as a participant in the regulation of fear response. It suggests that PRDX6 and related molecules may have important implications for understanding fear-dysregulation associated disorders like PTSD.
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    Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity
    (2021-12-01) Sarayut Phasuk; Sureka Jasmin; Tanita Pairojana; Hsueh Kai Chang; Kai Chi Liang; Ingrid Y. Liu; Siriraj Hospital; Academia Sinica, Institute of Biomedical Sciences; Tzu Chi University
    Abstract: Peroxiredoxin 6 (PRDX6) is expressed dominantly in the astrocytes and exerts either neuroprotective or neurotoxic effects in the brain. Although PRDX6 can modulate several signaling cascades involving cognitive functions, its physiological role in spatial memory has not been investigated yet. This study aims to explore the function of the Prdx6 gene in spatial memory formation and synaptic plasticity. We first tested Prdx6−/− mice on a Morris water maze task and found that their memory performance was defective, along with reduced long-term potentiation (LTP) in CA3-CA1 hippocampal synapses recorded from hippocampal sections of home-caged mice. Surprisingly, after the probe test, these knockout mice exhibited elevated hippocampal LTP, higher phosphorylated ERK1/2 level, and decreased reactive astrocyte markers. We further reduced ERK1/2 phosphorylation by administering MEK inhibitor, U0126, into Prdx6−/− mice before the probe test, which reversed their spatial memory deficit. This study is the first one to report the role of PRDX6 in spatial memory and synaptic plasticity. Our results revealed that PRDX6 is necessary for maintaining spatial memory by modulating ERK1/2 phosphorylation and astrocyte activation. Graphic Abstract: [Figure not available: see fulltext.]
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    The role of galectins in virus infection - A systemic literature review
    (2019-01-01) Wen Hung Wang; Chih Yen Lin; Max R. Chang; Aspiro Nayim Urbina; Wanchai Assavalapsakul; Arunee Thitithanyanont; Yen Hsu Chen; Fu Tong Liu; Sheng Fan Wang; Kaohsiung Medical University Chung-Ho Memorial Hospital; Chulalongkorn University; Academia Sinica, Institute of Biomedical Sciences; Mahidol University; National Chiao Tung University Taiwan; Kaohsiung Medical University
    © 2019 Background: Galectins are β-Galactose binding lectins expressed in numerous cells and play multiple roles in various physiological and cellular functions. However, few information is available regarding the role of galectins in virus infections. Here, we conducted a systemic literature review to analyze the role of galectins in human virus infection. Methods: This study uses a systematic method to identify and select eligible articles according to the PRISMA guidelines. References were selected from PubMed, Web of Science and Google Scholar database covering publication dated from August 1995 to December 2018. Results: Results indicate that galectins play multiple roles in regulation of virus infections. Galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-8 (Gal-8), and galectin-9 (Gal-9) were found as the most predominant galectins reported to participate in virus infection. The regulatory function of galectins occurs by extracellularly binding to viral glycosylated envelope proteins, interacting with ligands or receptors on immune cells, or acting intracellularly with viral or cellular components in the cytoplasm. Several galectins express either positive or negative regulatory role, while some had dual regulatory capabilities on virus propagation based on the conditions and their localization. However, limited information about the endogenous function of galectins were found. Therefore, the endogenous effects of galectins in host-virus regulation remains valuable to investigate. Conclusions: This study offers information regarding the various roles galectins shown in viral infection and suggest that galectins can potentially be used as viral therapeutic targets or antagonists.
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    Success stories in genomic medicine from resource-limited countries
    (2015-01-01) Konstantinos Mitropoulos; Hayat Al Jaibeji; Diego A. Forero; Paul Laissue; Ambroise Wonkam; Catalina Lopez-Correa; Zahurin Mohamed; Wasun Chantratita; Ming Ta Michael Lee; Adrian Llerena; Angela Brand; Bassam R. Ali; George P. Patrinos; The Golden Helix Foundation; Maastricht University; College of Medicine and Health Sciences United Arab Emirates University; Universidad Antonio Nariño; Universidad del Rosario; University of Cape Town, Faculty of Health Sciences; Genome Quebec; University of Malaya; Mahidol University; Riken; Academia Sinica, Institute of Biomedical Sciences; Universidad de Extremadura; Panepistimion Patron
    © 2015 Mitropoulos et al. In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.