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:
- Establishment of brain bio-targeting technique.
- Blood brain barrier and targeted drug delivery system
- Therapeutic and diagnostic applications of brain bio-targeting.
- Application of high seed imaging technique for live cell imaging.
- Mechanism of microglial toxic change in brain disorders.
- Cell therapy with stem cells and/ or progenitor cells.
- Hirata Y, Yamada C, Ito Y, Yamamoto S, Nagase H, Oh-Hashi K, Kiuchi K, Suzuki H, Sawada M, Furuta K. Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells. Neuropharmacology 135: 242-252, 2018.
- Wu Q, Ono K, Suzuki H, Eguchi M, Yamaguchi S, Sawada M. Visualization of Arc promoter-driven neuronal activity by magnetic resonance imaging. Neurosci Lett 666: 92-97, 2018.
- Lin H, Muramatsu R, Maedera N, Tsunematsu H, Hamaguchi M, Koyama Y, Kuroda M, Ono K, Sawada M, Yamashita T. Extracellular lactate dehydrogenase a release from damaged neurons drives central nervous system angiogenesis. EBioMedicine 27:71-85, 2018.
- Oya M, Suzuki H, Anas ARJ, Oishi K, Ono K, Yamaguchi S, Eguchi M, Sawada M. LC-MS/MS imaging with thermal film-based laser microdissection. Anal Bioanal Chem 410(2): 491-499, 2018.
- Ono K, Suzuki H, Yamamoto R, Sahashi H, Takido Y, Sawada M. Optogenetic control of cell differentiation in channelrhodopsin-2-expressing OS3, a bipotential glial progenitor cell line. Neurochem Int 104: 49-63, 2017.
- Kawahara K, Hirata H, Ohbuchi K, Nishi K, Maeda A, Kuniyasu A, Yamada D, Maeda T, Tsuji A, Sawada M, Nakayama H. The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain. Glia 64(11):1938-1961, 2016.
- Matsumoto T, Takahashi N, Kojima T, Yoshioka Y, Ishikawa J, Furukawa K, Ono K, Sawada M, Ishiguro N, Yamamoto A. Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages. Arthritis Res Ther 18(1): 133, 2016.
- Biju V, Hamada M, Ono K, Sugino S, Ohnishi T, Shibu ES, Yamamura S, Sawada M, Nakanishi S, Shigeri Y, Wakida SI. Nanoparticles speckled by ready-to-conjugate lanthanide complexes for multimodal imaging. Nanoscale 7(36): 14829-14837, 2015.
- Mizoguchi H, Katahira K, Inutsuka A, Fukumoto K, Nakamura A, Wang T, Nagai T, Sato J, Sawada M, Ohira H, Yamanaka A, Yamada K. Insular neural system controls decision-making in healthy and methamphetamine-treated rats. Proc Natl Acad Sci USA 112(29): E3930-3939, 2015.
- Sumida M, Hane M, Yabe U, Shimoda Y, Pearce OM, Kiso M, Miyagi T, Sawada M, Varki A, Kitajima K, Sato C. Rapid trimming of cell surface polySia by exovesicular sialidase triggers release of preexisting surface neurotrophin. J Biol Chem 290(21):13202-13214, 2015.
(April 20th, 2018)