Graduate School of Frontier Sciences, The University of Tokyo Department of
Integrated Biosciences

We carry out research on cellular responses to internal and external environmental changes. Aging, for instance, is a prime example of a drastic internal environmental change. In recent years, Japan has faced problems such as a low birth rate and an aging society, which have become causes for concern. For this reason, we have dedicated ourselves to research on cognition and the elucidation of mechanisms responsible for dementia and cognitive disorders.　

It is well known that higher functions of the brain, such as memory and learning, decline as we age. As hippocampal networks play a prominent role in the processes of learning and memory, we have postulated that changes in these networks might start occurring with age.　While it has been discovered in recent years that new neurons are born in the adult hippocampus, it has also been seen that the number of these newborn neurons tends to decrease as we age. As such, there is a possibility that this decrease in the number of newborn neurons, which are intricately related to memory formation and maintenance (Fig. 1), might be a cause for the cognitive decline associated with aging. For this reason, by researching the properties of newborn neurons, we aim to elucidate how hippocampal networks function. In practical terms, concomitantly with elucidating the characteristics of synaptic connections, we are carrying out research in order to understand how deeply memory is reliant on hippocampal networks by examining the cognitive capabilities of mice in which newborn neurons have been eliminated through genetic manipulation.

As we get older, the prevalence of neurodegenerative diseases such as Alzheimer’s Disease tends to increase. In our laboratory, we have been developing methods to increase the number of newborn neurons in order to maintain normal cognitive functioning in aging animals by altering their lifestyle (i.e. learning, exercise, and dietary habits). Changes in lifestyle are capable of helping prevent Alzheimer’s, as evidenced by immunological studies. Based on these studies, we aim to understand why cognitive decline occurs as we age and why lifestyle affects cognition, and by doing so, develop new strategies to prevent Alzheimer’s Disease.

By utilizing Alzheimer’s Disease model animals, (Fig. 2) and new medical imaging techniques (MRI), we are undertaking research aiming to develop new strategies for the prevention and treatment of cognitive disorders.

Left:

Fig. 1. Hippocampal networks and newborn neurons. (a) Location of the hippocampus in the adult mouse. (b) Hippocampal network and new neurons (green).

Right:

Fig. 2. Alzheimer's Disease model mouse. Hippocampus of an Alzheimer's Disease model mouse. Senile plaques and glial neuroinflammation in the hippocampus.

Our current research topics are as follows.

Until now, it was believed that the number of neurons only decrease as we age. However, in these last years, we got evidence that contradicts that established theory. We learned that in the hippocampus, a part of the brain related to memory, new neurons are always being born and changing, even in adults. Through the use of mice and monkeys, we are conducting research to physiologically and biochemically understand the phenomenon of neurogenesis. Furthermore, our results show that this neurogenesis in the hippocampus is related to learning and memory. As it is known that hippocampal neurons fade away at an exponential rate as we reach old age, we aim to a way to improve the rate of neurogenesis in the aging brain, and in doing so, improve the brain health of our aging society.

In an aging society like ours, diseases and complications related to old age are starting to become a serious social problem. As we age, the risk of neurological disorders such as ischemia or Alzheimer’s disease gets higher. The goal of our research is to find a way to restore functionality to damaged areas of the brain, through the use of techniques that induce the phenomenon of neurogenesis in adult brains. By using mice and monkey ischemia models, we are aim to understand the foundation of neurogenesis.

As we age, for some reason our brains start to lose their functionality. Why is that so? In order to answer that question, we are conducting research with aged animals. Maybe the reason for that change is in the brain cells themselves, or maybe the blood vessels in the brain have something to do with it? To understand that, we are carrying out an analysis using brain imaging techniques. As we age, some changes occur in the blood vessels in our brain, as evidenced by the hardening of arteries, and with that, the risk of thrombosis and embolism tend to increase. To learn how to prevent the closing of small blood vessels in the brain, the reason for lacunar brain infarcts, we are researching this phenomenon using animal models.