Objective To observe the effect of pre-moxibustion at “Baihui”(GV20)

“Shenshu”(BL23) and “Zusanli”(ST36) on expression of Tau protein and related protein kinases as glycogen synthase kinase-3β(GSK-3β)

etc. in the hippocampal CA3 region of Alzheimer's disease(AD) rats

so as to explore its mechanism underlying prevention and treatment of AD cognitive impairment. Methods Male SD rats were randomly divided into 4 groups: normal control

sham operation

model and pre-moxibustion

with 9 rats in each group. Rats of the pre-moxibustion group received moxibustion of GV20

BL23 and ST36 for 15 min

once a day

6 days a week for 3 weeks. After completion of moxibustion

the AD model was reproduced by injection of amyloid beta-peptide 25-35(Aβ 25-35) aggregation solution 1 μL(5 μg/μL) into the bilateral hippocampus

rats of the sham operation group received injection of the same dose of normal saline into the hippocampus. The spatial learning-memory ability was detected using Morris water maze test

and changes of the ultrastructure of hippocampal neurons were observed using electron microscope

and those of histopathological changes of hippocampus tissue observed using hematoxylin eosin(H.E.) staining. The expression levels of hippocampal GSK-3β

p-Tau

CDK5 and Synapsin I proteins were detected by Western blot and immunohistochemistry

respectively. Results No significances were found between the normal control and sham groups in all the indexes(P>0.05). Compared with the control group

the escape latency of place navigation test of Morris water maze test

expression of GSK-3β and CDK5 and the immunoactivity of GSK-3β

CDK5 and p-Tau were significantly increased(P<0.01)

and the residence time in the platform quadrant and the number of platform crossing of spatial prob test and the expression of Synapsin Ⅰ significantly reduced in the model group(P<0.01). Following the intervention

the increase of escape latency

expression of GSK-3β and CDK5 and the immunoactivity of GSK-3β

CDK5 and p-Tau

and the decrease of residence time in the platform quadrant

number of platform crossing and the expression of Synapsin Ⅰ were reversed in the pre-moxibustion group(P<0.05

P<0.01). Outcomes of ultrastructure and histopathological observations respectively showed edema of hippocampal nerve cells at varying degrees

moderate edema of the cytoplasma

chromatin condensation at the edge of the nucleus

partial mitochondrial vacuole-like degeneration

fracture of tubular crest

edema and expansion of Golgi body

disappearance of polarity

fracture of the rough endoplasmic reticulum

degeneration of ribosome and partial myelin axon and reduced synaptic vesicles in the presynaptic capsule; and reduced number of neurons with shrank body

disappearance of nucleolus and blurred nuclear boundary and vacuole-like degeneration in some of them in the model group

which were relatively milder in the pre-moxibustion group. Conclusion Pre-moxibustion at GV20

BL23 and ST36 plays a role in slowing down the occurrence and development of cognitive impairment in AD rats

which may be related to its functions in inhibiting tau protein hyperphosphorylation and reducing the expression of some related protein kinases in the hippocampus.