Combination of auricular needling and nerve growth factor treatment improves learning and memory abilities in Alzheimer's disease model rats

Abstract

Objective To investigate the effect of combined auricular needling and nerve growth factor (NGF) treatment on learning and memory abilities of Alzheimer's disease (AD) model rats, as well as their possible mechanisms. Methods Forty male SD rats were randomly assigned into four groups: normal control group, AD model group, auricular needling group, and combined auricular needling and NGF treatment group. Okadaic acid was injected into the hippocampal CA1 region of rats to establish AD models, simultaneously, 5 μL NGF (0.1 g/L) was injected into the lateral ventricle of cerebrum for 5 times every other day while acupuncture at ear-kidney-brain auricular points was implemented as well. Morris Water Maze behavioral test was performed to assess the learning and memory abilities of the rats. The neuron apoptosis of the hippocampus was detected by flow cytometer. The expressions of glial fibrillary acidic protein (GFAP) and choline acetyl-transferase (ChAT) were examined by immunohistochemistry. The neurofibrillary tangle (NFT) was observed through Bielschowsky staining of the hippocampus, and Western blotting was used to observe the Tau protein hyperphosphorylation at Ser396 locus. Results As compared with auricular needling group, the combined auricular needling and NGF treatment group had significantly shortened average escape latency in place navigation test, prolonged active time in the third quadrant in spatial probe test, increased number of platform-crossing, decreased apoptosis ratio, decreased GFAP expression and NFT in the hippocampal CA1 region, increased ChAT expression in hippocampal CA1 region, and decreased phosphorylated Tau expression at the site of Ser396 (P<0.05). Conclusion (1) Acupuncture at Ear-Kidney-Brain auricular points combined with NGF obviously improves the learning and memory abilities of the model rats; and it is more effective than auricular needling alone. (2) The mechanisms might be related with reduced neurons apoptosis, decreased abnormal activation and hyperplasia of astrocyte, improved central cholinergic system functions, and inhibited hyperphosphorylated Tau expressions. Key words: Alzheimer's disease; Auricular needling; Nerve growth factor; Tau protein