Objective

2

To explore the effect of

Tongdu Jieyu

acupuncture (acupuncture for promoting the circulation of the governor vessel and relieving depression) on hippocampal neuronal damage in post-stroke depression (PSD) rats based on the neuregulin 1 (NRG1)/epidermal growth factor receptor 4 (ErbB4) pathway.

Methods

2

Ninety-five SPF male rats were selected and randomly divided into a sham-operation group (15 rats) and an operation group (80 rats). Using Longa's suture-occluded method and chronic unpredictable mild stress method

PSD rat models were prepared. A total of 75 successfully modeled rats were randomly divided into a model group

an acupuncture group

a paroxetine group

a dacomitinib (ErbB4 inhibitor) group

and an acupuncture+dacomitinib group

with 15 rats in each one. In the acupuncture group

acupuncture was delivered at "Baihui" (GV20)

"Shenting" (GV24)

and bilateral "Neiguan" (PC6) and "Taichong" (LR3); and the electric stimulation with electroacupuncture instrument was exerted at "Neiguan" (PC6) and "Taichong" (LR3) on the same side

using continuous wave

at a frequency of 2 Hz

and an intensity of 0.1 mA to 1 mA

for 30 min in each intervention. In the paroxetine group

the intragastric administration was given with paroxetine

5 mg/kg; and in the dacomitinib group

the intragastric administration was given with dacomitinib

7.5 mg/kg. In the acupuncture+ dacomitinib group received the same interventions as the acupuncture group and the dacomitinib group. The above intervention measures were delivered once a day for consecutive 28 days in each group. Longa's score was compared

and the behavior of rats was observed using the open field test and sucrose preference test in each group. Using ELISA method

the hippocampal levels of malonaldehyde (MDA)

catalase (CAT)

5-hydroxytryptamine (5-HT)

dopamine (DA)

and norepinephrine (NE) were detected. With HE staining and Nissl staining adopted

the hippocampal neuron morphology was observed. Golgi staining was employed to observe the morphological changes of dendritic spines in the hippocampal neurons. Immunohistochemistry was used to observe the positive expression of brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN1) in the hippocampal tissue

and Western blot was used to detect the protein expression of NRG1 and ErbB4 in the hippocampal tissues.

Results

2

Compared with the sham-operation group

the Longa's score and hippocampal MDA level in the model group increased (

P

<

0.05)

while the decrease was presented in the number of horizontal crossing grids score

vertical movement score

sucrose consumption percentage; the levels of CAT

5-HT

DA and NE

the positive expression rates of BDNF and SYN1

and the protein expression of NRG1 and ErbB4 in the hippocampal tissue (

P

<

0.05). Besides

the hippocampal neurons were disarranged

with karyopyknosis presented; Nissl's bodies were dissolved and lost

and the average length of synaptic spines was shortened in the model group (

P

<

0.05). When compared with the model group

the above indicators were ameliorated in the acupuncture group and paroxetine group (

P

<

0.05). The results of these indexes in the acupuncture+dacomitinib group were inferior to the acupuncture group

but superior to the dacomitinib group (

P

<

0.05).

Conclusion

2

Tongdu Jieyu

acupuncture alleviates hippocampal neuronal damage and attenuates PSD in rats

which is obtained probably by activating the NRG1/ErbB4 pathway.