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J.Health Sci., 50(5), 429-442, 2004
-Review-
Analysis of Brain Function and Prevention of Brain Diseases: the Action of Trace Metals
Atsushi Takeda*
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526,
Japan
Trace metals such as zinc, manganese, and iron are necessary for the growth and function of the brain. The
transport of trace metals into the brain is strictly regulated by the brain barrier system,
i.e., the blood-brain and blood-cerebrospinal fluid barriers. The alteration of homeostasis of trace metals in the brain is associated with brain
diseases. Trace metals usually serve the function of metalloproteins in neurons and glial cells, while a portion of
trace metals exists in the presynaptic vesicles and may be released with neurotransmitters into the synaptic cleft.
Zinc and manganese influence the concentration of neurotransmitters in the synaptic cleft, probably
via the action against neurotransmitter receptors and transporters and ion channels. Zinc may be an inhibitory neuromodulator of
glutamate release in the hippocampus, while neuromodulation by manganese might have both functional and toxic
aspects in the synapse. Dietary zinc deficiency affects zinc homeostasis in the brain, followed by an enhanced
excitotoxicity of glutamate in the hippocampus. Transferrin may be involved in the physiologic transport of iron and
manganese into the brain and their utilization there.
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