Innervation from the entorhinal cortex to the dentate gyrus and the vulnerability to Zn2.
Hippocampal Zn2+homeostasis is critical for cognitive activity and hippocampus-dependent memory. Extracellular Zn2+signaling is linked to extracellular glutamate signaling and leads to intracellular Zn2+signaling, which is involved in cognitive activity. On the other hand, excess intracellular Zn2+signaling that is induced by excess glutamate signaling is involved in cognitive decline. In the hippocampal formation, the dentate gyrus is the most vulnerable to aging and is thought to contribute to age-related cognitive decline. The layer II of the entorhinal cortex is the most vulnerable to neuronal death in Alzheimer's disease. The perforant pathway provides input from the layer II to the dentate gyrus and is one of the earliest affected pathways in Alzheimer's disease. Medial perforant pathway-dentate granule cell synapses are vulnerable to either excess intracellular Zn2+or β-amyloid (Aβ)-bound zinc, which induce transient cognitive decline via attenuation of medial perforant pathway LTP. However, it is unknown whether the vulnerability to excess intracellular Zn2+is involved in region-specific vulnerability to aging and Alzheimer's disease. To discover a strategy to prevent short-term cognitive decline in normal aging process and the pre-dementia stage of Alzheimer's disease, the present paper deals with vulnerability of medial perforant pathway-dentate granule cell synapses to intracellular Zn2+dyshomeostasis and its possible involvement in differential vulnerability to aging and Alzheimer's disease in the hippocampal formation.
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: takedaa@u-shizuoka-ken.ac.jp.
Atsushi
A
Takeda
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Hanuna
H
Tamano
D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism*; D018728:Entorhinal Cortex / Q000737:chemistry / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015032:Zinc / Q000378:metabolism*
D015032:Zinc
Cognition; Entorhinal cortex; Hippocampus; Perforant pathway; Zinc; β-amyloid