The present study aimed to investigate the effect of the long non-coding rna antisense non-coding rna in the inK4 locus (lnc-anril) knockdown on apoptosis, neurite outgrowth and inflammation based on a PC12 cellular alzheimer's disease (ad) model. a cellular ad model was constructed by treating nerve growth factor stimulated PC12 cells with amyloid β (aβ) 1-42 and then control knockdown plasmid and lnc-anril knockdown plasmid were transfected in the Pc12 cellular ad model as the Kd-negative control (nc) group or the ad-anril group respectively. Apoptosis, neurite outgrowth, pro-inflammatory cytokines and microrna (mir)-125a were assessed. rescue experiments were conducted by transfecting lnc-ANRIL knockdown plasmid and lnc-anril knockdown plasmid and mir-125a inhibitor in the PC12 cellular AD model as the KD-ANRIL group or Kd-anril + Kd-mir-125a group respectively. Following transfection, cell apoptosis deccreased while neurite outgrowth increased in the Kd-anril group compared with the Kd-nc group (all P<0.01). concerning inf lammation, tumor necrosis factor-α (TnF-α) and interleukin (il)-1β, il-6 and il-17 were decreased in the Kd-anril group compared with the Kd-nc group (all P<0.01). miR-125a was negatively regulated by lnc-ANRIL and therefore rescue experiments were subsequently conducted. in the rescue experiments, cell apoptosis was increased while total neurite outgrowth was inhibited in the Kd-anril + Kd-mir-125a group compared with the Kd-anril group (all P<0.01), and TnF-α, il-1β, il-6 and il-17 were increased in the Kd-anril + Kd-mir-125a group compared with the Kd-anril group (all P<0.01). a luciferase reporter assay demonstrated that lnc-ANRIL directly bound miR-125a. lnc-ANRIL knockdown suppressed cell apoptosis and inflammation while promoting neurite outgrowth via binding of miR-125a in AD.

IntroductionThe degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice.MethodsThree-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aβ, Bcl-2/Bax were determined by immunohistochemistry and western blot.ResultsAPP/PS1 mice not only had increased Aβ accumulation, impaired memory performance, less synapse number, and much more necrosed neurons, but also had significant reduction in the Bcl-2/Bax ratio. However, GAPT and donepezil showed improved memory performance, less Aβ accumulation, increased neuron and synapse number, as well as restored balance of Bcl-2/Bax.DiscussionGAPT may improve cognitive functions via both reducing Aβ deposition and restoring Bcl-2/Bax balance of neuron.

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