Blockage of metallothionein synthesis via adrenaline β receptor activation invalidates dehydroeffusol-mediated prevention of amyloid β toxicity.

Dehydroeffusol, a major phenanthrene in Juncus effusus, protects neurodegeneration induced by intracellular Zn ferried by extracellular amyloid β (Aβ). Here we focused on adrenaline β receptor activation and the induction of metallothioneins (MTs), intracellular Zn-binding proteins to test the protective mechanism of dehydroeffusol. Isoproterenol, an agonist of adrenergic β receptors elevated the level of MTs in the dentate granule cell layer 1 day after intracerebroventricular (ICV) injection.

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.

Dehydroeffusol Rescues Amyloid β-Induced Spatial Working Memory Deficit.

Amyloid β (Aβ) peptides produced from the amyloid precursor protein, a transmembrane protein, are neurotoxic and blocking the neurotoxicity may lead to prevention of Alzheimer's disease (AD). Here we tested whether Aβ-induced cognitive decline is rescued by treatment with dehydroeffusol, a phenanthrene isolated from Chinese medicine Juncus effusus. Dehydroeffusol (5 ~ 15 mg/kg body weight) was orally administered to mice for 6 days and Aβ (2 mM) was injected at the rate of 1 μl/min for 3 min into the lateral ventricle.

Extracellular Zn-Dependent Amyloid-β Neurotoxicity in Alzheimer's Disease Pathogenesis.

The basal level of extracellular Zn is in the range of low nanomolar (~ 10 nM) in the hippocampus. However, extracellular Zn dynamics plays a key role for not only cognitive activity but also cognitive decline. Extracellular Zn dynamics is modified by glutamatergic synapse excitation and the presence of amyloid-β (Aβ), a causative peptide in Alzheimer's disease (AD).

Preferential Neurodegeneration in the Dentate Gyrus by Amyloid β-Induced Intracellular ZnDysregulation and Its Defense Strategy.

On the basis of the evidence that rapid intracellular Zn dysregulation by amyloid β (Aβ) in the normal hippocampus transiently induces cognitive decline, here we report preferential neurodegeneration in the dentate gyrus by Aβ-induced intracellular Zn dysregulation and its defense strategy. Neurodegeneration was preferentially observed in the dentate granule cell layer in the hippocampus after a single Aβ injection into the lateral ventricle but not in the CA1 and CA3 pyramidal cell layers, while intracellular Zn dysregulation was extensively observed in the hippocampus in addition to the dentate gyrus. Neurodegeneration in the dentate granule cell layer was rescued after co-injection of extracellular and intracellular Zn chelators, i.

CA1 LTP Attenuated by Corticosterone is Canceled by Effusol via Rescuing Intracellular Zn Dysregulation.

Exposure to corticosterone attenuates hippocampal CA1 long-term potentiation (LTP) via intracellular Zn dysregulation. Here we report that effusol, a phenanthrene isolated from Chinese medicine Juncus effusus, rescues CA1 LTP attenuated by corticosterone. In vivo microdialysis experiment indicated that both increases in extracellular glutamate induced under perfusion with corticosterone and high K are suppressed in the hippocampus by co-perfusion with effusol.

Extracellular Zn-independently attenuated LTP by human amyloid β and rat amyloid β.

Human amyloid-β (Aβ) and rat Aβ have lower affinity for extracellular Zn than human Aβ. Here we report extracellular Zn-independent attenuation of dentate gyrus long-term potentiation (LTP) by human Aβ and rat Aβ. On the basis of the data that dentate gyrus LTP is extracellular Zn-dependently attenuated after local injection of human Aβ (25 pmol, 1 μl) into the dentate gyrus, which increases intracellular Zn in the dentate gyrus, the toxicity of human Aβ and rat Aβ was compared in the in vivo system with human Aβ.