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Yamada Research Unit
Masahisa YAMADA
Unit Leader
Masahisa YAMADA (Ph.D.)
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Research Areas

The brain utilizes a remarkably large fraction of the body's energy resources at any given a moment the most active nerve cells use more glucose and oxygen than relatively quiescent neurons. The blood supply of brain is particularly significant because neurons are so sensitive to oxygen deprivations as well as to altered concentrations of other substances. Whereas reduced cerebral blood flow (CBF) is commonly observed in elderly population, the relationship between the influence of that energy supply and aging remained obscure, especially mechanism of developing dementia does not yet fully understand. We focus on an influence of reduced energy supply on synaptic changes of neuronal network. This laboratory revealed involvement of muscarinic acetylcholine receptor signaling at CBF regulation and now investigating the endothelial-glial allegiance of blood-brain barrier (BBB). The interface between the walls of capillaries and surrounding tissue is important throughout the body, as it allow ionic and molecular traffic. More recently we are developing and applying innovate cell transplantation techniques based on modulation of the fate determination of mouse embryonic stem cells. We apply these techniques for medical application of the neurovascular related dysfunction of neural network.

Research Subject

  1. Vascular endothelial cells and cognitive brain function
  2. Neuro-glio-vascular interactions and brain function
  3. Development of drug delivery system
  4. Roles of BMP in cerebellar neuronal network

Press release

April 10, 2009
Elucidation of the partial effect of the female hormone estrogen on memory improvement: Gender differences following transgenic treatment of patients with chronic brain circulatory disturbance suggests stronger tolerance to brain lesions in the female brain than in the male brain.

List of Selected Publications

  1. Yamada, M., Kishida, H.,and Kitamura, N.:
    "Astrocytic bone morphogenetic protein signaling modulates the functional blood-brain-barrier."
    Trends in Dev. Biol. in press
  2. Kitazawa, T., Hirama, R., Masunaga, K., Nakamura, T., Asakawa, K., Cao, J., Teraoka, H., Unno, T., Komori, S., Yamada, M., Wess, J.,and Taneike, T.:
    "Muscarinic receptor subtypes involved in carbachol-induced contraction of mouse uterine smooth muscle."
    Naunyn Schmiedebergs Arch Pharmacol. 377(4-6), 503-513, 2008.
  3. Araya, R., Kudoh, M., Kawano, M., Ishii, K., Hashikawa, T., Iwasato, T., Itohara, S., Terasaki, T., Oohira, A., Mishina, Y.,and Yamada M.:
    "BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier."
    Mol.Cell.Neurosci. 38(3) ,417-430, 2008 .
  4. Khalil, IA., Kogure, K., Futaki, S., Hama, S., Akita, H., Ueno, M., Kishida, H., Kudoh, M., Mishina, Y., Kataoka, K., Yamada, M.,and Harashima, H.:
    "Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery."
    Gene Therapy . 14, 682-689, 2007
  5. Yamada, M., Tanemura, K., Okada, S., Iwanami, A., Nakamura, M., Mizuno, H., Ozawa, M., Ohyama-Goto, R., Kitamura, N., Kawano, M., Tan-Takeuchi, K., Ohtsuka, C., Miyawaki, A., Takashima, A, Ogawa, M., Toyama, Y., Okano, H.,and Kondo, T.:
    "Electrical stimulation modulates fate determination of differentiating embryonic stem cells."
    Stem Cells. 25 (3) , 562-570 , 2007
  6. Fukuda,T., Scott, G., Komatsu, Y., Araya, R., Kawano, M., Ray, MK., Yamada, M., and Mishina, Y.:
    "Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2."
    Genesis. 44(4), 159-167, 2006
  7. Araya, R., Noguchi, T., Yuhki, M., Kitamura, N., Higuchi, M.,Saido, TC., Seki, K., Itohara, S., Kawano, M., Tanemura, K., Takashima, A.,Yamada, K., Kondoh, Y., Kanno, I., Wess, Jand.,and Yamada, M.:
    "Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice."
    Neurobiology of Disease. 24(2), 334-344, 2006
  8. Yuhki, M., Yamada, M., Kawano, M., Iwasato, T., Itohara ,S., Yoshida ,H., Ogawa, M., and Mishina, Y.:
    "BMP receptor IA signaling is necessary for hair follicle cycling and hair shaft differentiation in mice,"
    Development, 131, 1825-1833, 2004.
  9. Basile, A.S., Fedorova, I., Zapata, A., Liu, X., Shippenberg, T., Duttaroy, A., Yamada, M.and, Wess J.:
    "Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia."
    Proc. Natl. Acad. Sci. USA, 99, 11452-11457, 2002.
  10. Fisahn, A., Yamada, M., Duttaroy, A., Gan, J.W., Deng, C.X., McBain, C.J.,and Wess, J,:
    "Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents,"
    Neuron, 33, 615-624, 2002.
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