Ninjinyoeito reduces β‐amyloid25–35‐induced axon damage via nerve growth factor

Abstract

AbstractAimNinjinyoeito (NYT), a Japanese herbal medicine, is widely used to treat patients with insomnia, anemia, amnesia, and neurosis. Recently, NYT was reported to be clinically effective in Alzheimer's disease (AD). We investigated the effects of NYT in a neurodegeneration model comprising cultured autaptic neurons exposed to β‐amyloid (Aβ)25–35.MethodsWe used an autaptic culture system consisting of a single neuron on astrocyte feeder micro‐islands. The effects of NYT (0.1 mg/ml) on neurotoxicity induced by Aβ25–35 (1 μmol/L) were assessed by immunocytochemical assays and Sholl analysis of microtubule‐associated protein 2 (MAP2)‐positive and tau‐positive neurites. Nerve growth factor (Ngf) and brain‐derived neurotrophic factor (Bdnf) gene expression were examined in primary cocultured astrocytes and neurons using reverse transcription polychromatic chain reaction (RT‐PCR).ResultsAβ25–35 treatment attenuated the arborization of axons and dendrites of single autaptic hippocampal neurons in a concentration‐dependent manner. NYT treatment for three days ameliorated the Aβ25–35‐induced impairment of tau‐positive axon outgrowth. However, NYT did not ameliorate the Aβ25–35‐induced suppression of MAP2‐positive dendrite arborization. NYT increased the expression of Ngf but not Bdnf in Aβ25–35‐exposed primary cocultured astrocytes and neurons.ConclusionWe propose a new model of neurodegeneration in which dendrite and axon outgrowth in autaptic neuronal cultures is inhibited by Aβ25–35. Our results indicate that NYT protects against Aβ25–35‐induced neuronal injury through induction of nerve growth factor expression. These findings provide a mechanistic basis for treating AD with NYT.