Juntendo University, Tokyo, established in 1838.

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University Research Institute for Diseases of Old Age

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Introduction

Welcome to the Juntendo University School of Medicine, Research Institute for Diseases of Old Age

The Research Institute for Diseases of Old Age in Juntendo University was established in 2000 as a part of the five-year project supported by a National Grant-in-Aid for the Establishment of High-Tech Research Centers in Private Universities from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The missions of this institute are to elucidate the mechanisms underlying diseases affecting elderly people, and to develop new treatment strategies that can stop or delay the disease processes. We have three major goals that include 1) elucidating the cause of Parkinson's disease and development of a new treatment that stops the disease process, 2) elucidating the causes of dementing disorders particularly Alzheimer's disease, and 3) exploring the neuronal mechanisms of higher cerebral functions and age-related decline of those functions.

 To achieve these purposes, we encourage collaborative studies and promote international research projects. The institute, 8,661.49 square meter spaces in a 12 floor-building, is equipped with all the instruments necessary for the most recent molecular biological studies and neurophysiologic investigations. Major equipment includes DNA sequencers, confocal laser fluorescence microscopes, an evanescent microscope, a laser microdissection, DNA microarray systems, a sequence detector protein sequencer, a mass spectrometer, etc.

 Anyone who is interested in the above projects can use our facilities as a collaborative investigator.

Parkinson' Disease Section

We have contributed a lot to the understanding of molecular mechanism of nigral neuronal death in familial forms of Parkinson's disease. Our group identified one of the causative genes for familial Parkinson's disease, parkin, the causative gene for an autosomal recessive form of young onset familial Parkinson's disease (Nature 1998).

Research is also directed toward elucidating the cellular mechanisms underlying neuronal injury and death in sporadic PD, and developing therapeutic countermeasures. We are especially interested in gene therapy using AAV vector and the analysis of the neurogenesis in Parkinson’s disease. Recently, we found that Neuronal reconstruction is involved with Parkinson's disease (Reuters Press 2005-07-22)

Stroke Section

In the stroke area, we are studying pathophysiology of ischemic neuronal damage and prevention using cellular and animal models. Our research includes apoptosis, regeneration, migration of neurons, and angiogenesis in stroke.

We also have a group working on neuromuscular disorders. We are particularly interested in the role of the extracellular matrix such as laminin and perlecan basement membranes in muscle disorders. We also use a transgenic model mouse aimed at the creation of a new therapy.

Our department covers most of the exciting areas in neurology and neuroscience and worldwide collaborative projects are going on.

Alzheimer's Section

One of the main studies in the department of Psychiatry is bio-psycho-social investigation on Alzheimer's disease (AD). This project is based on the out-patients' clinic for younger patients with AD in the Juntendo Unversity Hospital. The main study is genetic examinations to find out new risk factors for developing AD. Another study is a neuropathological one on postmortem brains obtained from AD patients. In terms of heterogeneity of AD, we are also collecting clinical and psychosocial information to examine the correlations between such factors and biological findings. Radiological investigations using single photon emmision computed tomography (SPECT) are also being completed to find more about the very early stage of AD. Clinical pharmacological intervention and the correlations between drug efficacy and genetic factors are also under investigation.

Higher Brain Function Section

1) Optimization of goal-directed movements:
Voluntary goal-directed movements, such as arm reaching, are nearly optimized in terms of smoothness over the entire movement. Such smoothness is lost with cerebellar dysfunction, suggesting the essential role of the cerebellum in optimizing movement. However, how the cerebellum contributes to achieving smoothness over an entire movement is not clear. We have recently proposed a random walk hypothesis (Kitazawa 2002) that the terminal errors conveyed by climbing fibers in the cerebellum (Kitazawa et al. 1998) serve to reduce not only the mean error, but also the variance of the error, through a process analogous to the random walk through movement control candidates. We are planning electrophysiological experiments for testing this hypothesis.

2) Neural representation of temporal order and simultaneity:
The brain is generally accepted to be able to resolve the order of two stimuli that are separated by time in as little as 30 ms. This basically applies to temporal order judgments where two separate tactile stimuli are delivered to each hand, as long as the arms remain uncrossed. However, we recently found that crossing the arms caused many subjects to misreport (that is, invert) the temporal order (Yamamoto and Kitazawa 2001a). When the stimuli were delivered to the tips of sticks held in each hand, the judgment was dramatically altered by crossing the sticks without changing the positions of the hands (Yamamoto and Kitazawa 2001b). We suggest that unless the sensory signals are referred to relevant locations in space, which could be the hand itself or the tip of the stick in hand, the stimuli are ordered in time. We are further examining the neural representation of temporal order with animals that are trained to judge temporal order of tactile stimuli.

3) The role of dopamine and serotonin in the basal ganglia:
Monoaminerigic neurons (dopamine, serotonin) are known to be very important in learning, but their roles are still not characterized enough. Using in vivo voltammetry system which enables simultaneous measurement of dopamine and serotonin at 4 Hz for more than one year, the role of these transmitters in learning is studied. Also, we study the mechanism of Parkinson's disease from the neuropharmacological aspects, and study the function of trace amine (tyramine) in the brain.

4) Neural Mechanisms of Visual Perception:
Understanding the neural mechanisms of visual perception is a major challenge in cognitive neuroscience. In this lab, we study the perception of motion and depth using psychophysical and neurophysiological methods. Our aim is to understand how visual information is encoded in the brain, and how they are read out to perform complex behavior.

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