Research Institute of Environmental Medicine Nagoya University

One of the experimental goal in our division is to understand the mechanisms of brain developmental anomalies. We have isolated the cDNA fragments of neuronal cell death control gene candidates. We also focus on the roles of microglia which are important cells in the development, differentiation and maintenance of neural cells. We have reported that microglia can be divided into sub　populations and have an affinity specific for the brain, which is clearly different from that of macrophages. We have established microglial cell lines; they can be transfected the expression vectors of the functional proteins such as cytokines, extracellular matrices or enzymes. We found that microglia had a specific affinity to the brain. Furthermore, peripherally injected microglia exhibit specific affinity for brain insults and do not exacerbate such neuronal injury. Rather we found protective effects of exogenous microglia on delayed death of pyramidal neurons. Therefore, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/or drugs for CNS repair following transitory global ischemic insult. We also analyze the brains from animals injected DNA-transfected microglia intra-aortically on several developmental stages to elucidate the stage-specific roles of these factors. Using this system, we have found that microglia have an important roles in development of brain higher functions such as learning and memory as well as structural formation.

The current projects of the department are as follows:

1. Establishment of brain bio-targeting technique.
2. Blood brain barrier and targeted drug delivery system
3. Therapeutic and diagnostic applications of brain bio-targeting.
4. Application of high seed imaging technique for live cell imaging.
5. Mechanism of microglial toxic change in brain disorders.
6. Cell therapy with stem cells and/ or progenitor cells.

1. Sobhanan J, Ono K, Okamoto T, Sawada M, Weiss PS, Biju V. Photosensitizer-singlet oxygen sensor conjugated silica nanoparticles for photodynamic therapy and bioimaging. Chem Sci 15(6): 2007-2018, 2024.
2. Ono K, Sato J, Suzuki H, Sawada M. Distribution of Signal Peptides in Microvesicles from Activated Macrophage Cells. Int J Mol Sci 24(15): 12131, 2023.
3. Ono K, Niwa M, Suzuki H, Kobayashi NB, Yoshida T, Sawada M. Calmodulin as a Key Regulator of Exosomal Signal Peptides. Cells 12(1): 158, 2023.
4. Ono K, Niwa M, Suzuki H, Kobayashi NB, Yoshida T, Sawada M. Signal Sequence-Dependent Orientation of Signal Peptide Fragments to Exosomes. Int J Mol Sci 23(6): 3137, 2022.
5. Yoshioka N, Tanaka M, Ochi K, Watanabe A, Ono K, Sawada M, Ogi T, Itoh M, Ito A, Shiraki Y, Enomoto A, Ishigami M, Fujishiro M, Ogawa Y, Suganami T. The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model. Biomed Pharmacother 140: 111738, 2021.
6. Ono K, Niwa M, Suzuki H, Kobayashi NB, Yoshida T, Sawada M. Secretion of signal peptides via extracellular vesicles. Biochem Biophys Res Commun 560: 21-26, 2021.
7. Nomura M, Toyama H, Suzuki H, Yamada T, Hatano K, Wilson AA, Ito K, Sawada M. Peripheral benzodiazepine receptor/18 kDa translocator protein positron emission tomography imaging in a rat model of acute brain injury. Ann Nucl Med 35(1): 8-16, 2021.
8. Wang L, Li M, Lin Y, Du S, Liu Z, Ju J, Suzuki H, Sawada M, Umezawa K. Inhibition of cellular inflammatory mediator production and amelioration of learning deficit in flies by deep sea Aspergillus-derived cyclopenin. J Antibiot 73(9):622-629, 2020.
9. Kawakubo M, Tanaka M, Ochi K, Watanabe A, Saka-Tanaka M, Kanamori Y, Yoshioka N, Yamashita S, Goto M, Itoh M, Shirakawa I, Kanai S, Suzuki H, Sawada M, Ito A, Ishigami M, Fujishiro M, Arima H, Ogawa Y, Suganami T. Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis-associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects. Sci Rep 10(1): 983, 2020.
10. Hirata Y, Ito Y, Takashima M, Yagyu K, Oh-hashi K, Suzuki H, Ono K, Furuta K, Sawada M. Novel Oxindole-Curcumin Hybrid Compound for Antioxidative Stress and Neuroprotection. ACS Chemical Neurosci 11(1): 76-85, 2020.

(April 20th, 2018)