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Neuromolecular Dynamics Team / Molecular Neuroimaging Program

Introduction

The mission of the Neuromolecular Dynamics Team is to conduct neuroimaging research on animal models of neuropsychiatric illnesses in conjunction with multimodal technologies, including neuropathological, behavioral and electrophysiological analyses, leading to direct insights into early diagnosis and efficacious therapies of the diseases. In addition, our research projects are committed to elucidating molecular interactions that underlie visibility of neuroglial components in intravital neuroimaging.


Team Leader
Makoto Higuchi

Research Introduction

Alzheimer's disease and associated neurodegenerative disorders exhibit characteristic neuropathological alterations, but definite diagnoses of these diseases cannot be antemortemly made for living patients. Conversely, psychiatric conditions including depression and schizophrenia are clinically diagnosed on a symptomatic basis, although no hallmark lesions have been discovered in the postmortem brains of these illnesses. Several lines of hypotheses have attempted to link neuropathological changes and clinical manifestations, by focusing on specific molecules that may be implicated in neuronal injuries and consequently the onset of neuropsychiatric symptoms. The Molecular Neurobiology Team is engaged in the following projects on animal models providing potential evidence for such working theories:

(1) Amyloid hypothesis of Alzheimer's disease pathogenesis
Deposition of pathological fibrils termed amyloid is a hallmark lesion in the Alzheimer's disease brain, and it is hypothesized to induce neurodegeneration resulting in the clinical onset of the disease. This view is supported by the fact that genetically engineered mice overexpressing amyloidogenic molecules develop progressive loss of neuronal integrity, rationalizing our works on the establishment of diagnostic and therapeutic approaches targeting brain amyloidosis with the utility of these animal models.

(2) Monoamine hypothesis of psychiatric disorders
A body of evidence has indicated mechanistic association of altered monoamine (dopamine, serotonin, etc.) neurotransmissions with depression and schizophrenia. On this theoretical basis, we aim to unravel molecular events that are critically involved in the pathogenesis of these diseases, by reverse genetics techniques. Our current investigations include the in vivo imaging of mutant mice behaviorally recapitulating mental illnesses and the assessment of neurochemical and symptomatic changes in these animals following pharmacological interventions in monoamine neurotransmissions.

PET images of brain amyloid in the model mice. In contrast to low-level retention of radioactive signals in the normal mouse, progressive accumulation of amyloid in the brains of Alzheimer's disease models is observed as a function of age.

Mapping of dopamine D1 receptors in the living wild-type mouse brain. Intense expression of the receptors in the striatum is captured by PET.

Members

Makoto Higuchi
Team Leader
Hin Ki, Jun Maeda, Masahiro Maruyama, Naruhiko Sahara, Takashi Horiguchi
Senior Researcher
Maiko Ono, Masaki Tokunaga
Researcher
Takeharu Minamihisamatsu, Sayuri Sasaki
Tecnical Staff
Hiroyuki Kaneko, Barron Anna
Postdoctoral Fellow
Kana Osawa
Assistant
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