Water extract of Dendrobium nobile Lindl. alleviates learning and memory impairment through synaptic plasticity modulation and glial cell activation in APP/PS1 mice

Abstract:

Objective To explore whether the water extract of Dendrobium nobile Lindl.（DNL） can alleviate learning and memory impairment through synaptic plasticity modulation in APP/PS1 Alzheimer’s disease（AD） model in mice.Methods Twelve wild-type（WT） C57BL/6 male mice were randomly divided into two groups（n=6）：WT control group（WT） and DNL treatment alone group（WT+DNL，DNL was intragastrically administered at 10 mg/kg，once a day，for 2 months）. Twelve APP/PS1 mice were divided into two groups：APP/PS1 AD model group（APP/PS1） and APP/PS1 AD model treatment group（APP/PS1+DNL，APP/PS1 mice aged seven months received DNL intragastrically administered at 10 mg/kg，once a day，for two months）. Morris water maze was used to test the memory ability of the mice；Gorky staining was used to determine the number of dendritic spines in the hippocampus of the brain in the mice；electroencephalography was used to measure the long-term potentiation（LTP） in the hippocampus of the brain； immunohistochemical techniques were used to measure the expression of glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 in the hippocampus and evaluate the number of glial cells. The protein expression levels of Synapsin I，Synaptophysin，interleukin-6（IL-6），tumor necrosis factor-α（TNF-α），and interleukin-1β（IL-1β） in the hippocampus of the mice were measured by western blot.Results Compared with the WT group，the APP/PS1 group had a significantly increased escape latency on days 2-6，showing learning and memory dysfunction. In addition，compared with the WT group，the APP/PS1 group showed reductions in the number of dendritic spines and the expression levels of synapse-related proteins Synapsin I and Synaptophysin but noticeable increases in the number of astrocytes and microglial cells and the expression levels of inflammatory factors in the brain tissue. However，DNL treatment improved learning and memory function，inhibited the loss of dendritic spines and the decreases in synapse-related proteins Synapsin I and Synaptophysin in the APP/PS1 mice，alleviated the LTP injury of neurons in the hippocampal CA1 area，increased the numbers of astrocytes and microglial cells，and significantly downregulated the protein expression levels of inflammatory factors IL-6，TNF-α，and IL-1β.Conclusion The water extract of DNL may alleviate learning and memory dysfunction by inhibiting synaptic LTP in APP/PS1 mice.