Molecular and Cellular Mechanisms of Neurological Diseases
The mission of our research group is to elucidate the molecular and cellular mechanisms underlying psychiatric and neurodegenerative diseases. To this end, we aim to visualize the brain pathology and physiology of animal models by in vivo neuroimaging in combination with a variety of analyses such as molecular biology, pathology, physiology, and behavior. Utilizing advanced modalities of neuroimaging and neuromodulation, we also aim to develop novel technologies for early diagnosis and therapy of neurological disorders.
In vivo neuroimaging of pathophysiology in the model mice for neurological disorders
PET imaging of tau pathology in the brains of model mice and 3D distribution of phosphorylated tau accumulation in whole-brain tissue. (left panel). We aim to elucidate the pathophysiological dynamics of the model animal brain through multiscale imaging analysis by employing a variety of imaging techniques (right panel).
Establishment of methodologies to assess brain function and seed development for future therapy
A research platform has been developed to simultaneously assess brain activity and cognitive behavior in mouse models for neurological disorders, enabling investigation of the mechanisms underlying neural circuit dysfunction and evaluation of the therapeutic effects of novel drug candidates (left panel). By integrating approaches from pharmacology, genetics, and physics, we also aim to develop therapeutic approaches that can attenuate disease progression (right panel).
Member
Shimojo MasafumiGroup Leader
- Hirokawa Junya Principal Researcher
- Nakazono Tomoaki Researcher
- Matsushita Yumi Researcher
- Yanai Rin Researcher
- Endo Masaaki Researcher
- Koike Riki Postdoctoral Fellow
- Minamihisamatsu Takeharu Technical Staff
- Sasaki Sayuri Technical Staff
- Hayashi Sayaka Technical Staff
- Agu Anne Bernadette Salbador QST Research Assistant
- Inoue Ryuto QST Research Assistant
- Yao Zhiwei QST Research Assistant
- Nomura Yukiko Trainee
Concurrent member
- Tsukamoto Satoshi Section Manager
- Ishida Yuka Principal Technical Staff
- Aizawa Ryutaro Researcher
- Hiura Koki Researcher
Selected Publications
- Matsushita Y., Yoshida K., Yoshiya M., Shimizu T., Satoshi T., Kudo N., Takeuchi Y., Higuchi M., Shimojo M.: TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in mammalian brain. Proceedings of the National Academy of Sciences, 121 (50), e2404877121, (2024)
- Yanai R, Mitani TT, Susaki EA, Minamihisamatsu T, Shimojo M, Saito Y, Mizuma H, Nitta N, Kaneda D, Hashizume Y, Matsumoto G, Tanemura K, Zhang MR, Higuchi M, Ueda HR, Sahara N.: A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology. Brain Commun , 6 (5) , fcae326, (2024)
- Kudo T, Takuwa H, Takahashi M, Urushihata T, Shimojo M, Sampei K, Yamanaka M, Tomita Y, Sahara N, Suhara T, Higuchi M.: Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model. iScience , 26(4) , 106342 , (2023)
- Kimura T, Ono M, Seki C, Sampei K, Shimojo M, Kawamura K, Zhang MR, Sahara N,Takado Y, Higuchi M.: A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model. Eur J Nucl Med Mol Imaging , 49(13) , 4298-4311, (2022)
- Shimojo M, Ono M, Takuwa H, Mimura K, Nagai Y, Fujinaga M, Kikuchi T, Okada M, Seki C, Tokunaga M, Maeda J, Takado Y, Takahashi M, Minamihisamatsu T, Zhang MR, et al.: A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains. EMBO J , 40(22) , e107757, (2021)
- Maeda J, Minamihisamatsu T, Shimojo M, Zhou X, Ono M, Matsuba Y, Ji B, Ishii H, Ogawa M, Akatsu H, Kaneda D, Hashizume Y, Robinson JL, Lee VM, Saito T, Saido TC, Trojanowski JQ, Zhang MR, Suhara T, Higuchi M, Sahara N. Distinct microglial response against Alzheimer's amyloid and tau pathologies characterized by P2Y12 receptor. Brain Commun. , 3(1) , fcab011 , (2021).
- Osako Y, Ohnuki T, Tanisumi Y, Shiotani K, Manabe H, Sakurai Y, Hirokawa J.: Contribution of non-sensory neurons in visual cortical areas to visually guided decisions in the rat. Curr Biol, 31(13), 2757-2769 , (2021)
- Shimojo M, Takuwa H, Takado Y, Tokunaga M, Tsukamoto S, Minatohara K, Ono M, Seki C, Maeda J, Urushihata T, Minamihisamatsu T, Aoki I, Kawamura K, Zhang MR, Suhara T, Sahara N, Higuchi M.: Selective Disruption of Inhibitory Synapses Leading to Neuronal Hyperexcitability at an Early Stage of Tau Pathogenesis in a Mouse Model. J Neurosci, 40(17), 3491-3501, (2020)