Preventive effect of Ninjin-yoei-to, a Kampo medicine, on amyloid β-induced neurodegeneration via intracellular Zn toxicity in the dentate gyrus.

Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer's disease, here we examined the effect of NYT on amyloid β (Aβ)-induced neurodegeneration in the dentate gyrus. A diet containing 3% NYT was administered to mice for 2 weeks and human Aβ was intracerebroventricularly injected.

Dehydroeffusol Pprevents Amyloid β-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn Toxicity.

Dehydroeffusol, a phenanthrene isolated from Juncus effusus, is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer's disease, here we examined the effect of dehydroeffusol on amyloid β (Aβ)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aβ was injected intracerebroventricularly followed by oral administration for 12 days.

Retention Period of Amyloid β in the Brain Extracellular Fluid as the Toxicological Determinant in Freely Moving Rats.

The pathological significance of amyloid-β (Aβ) dynamics is poorly understood in the brain extracellular compartment. Here we test which of the concentration or the retention is critical for Aβ toxicity after injection of equal dose into dentate granule cell layer of freely moving rats. The toxicity of Aβ (25 µM) was compared between injections at the rate of 0.

Adrenergic β receptor activation reduces amyloid β-mediated intracellular Zn toxicity in dentate granule cells followed by rescuing impairment of dentate gyrus LTP.

Adrenergic β receptor activation prevents human soluble amyloid β (Aβ)-induced impairment of long-term potentiation (LTP) in slices. On the basis of the evidence that human Aβ-induced impairment of LTP is due to Aβ-mediated Zn toxicity, we postulated that adrenergic β receptor activation reduces Aβ-mediated intracellular Zn toxicity followed by rescuing Aβ toxicity. To test the effect of adrenergic β receptor activation, LTP was recorded at perforant pathway-dentate granule cell synapses of anesthetized rats 60 min after Aβ injection into the dentate granule cell layer.

In vivo synaptic activity-independent co-uptakes of amyloid β and Zn into dentate granule cells in the normal brain.

Neuronal amyloid β (Aβ) accumulation is considered an upstream event in Alzheimer's disease pathogenesis. Here we report the mechanism on synaptic activity-independent Aβ uptake in vivo. When Aβ uptake was compared in hippocampal slices after incubating with Aβ, In vitro Aβ uptake was preferentially high in the dentate granule cell layer in the hippocampus.