Objective

2

To observe the effects of electroacupuncture (EA) on high mobility group box-1 (HMGB1)/ receptor for advanced glycation end products (RAGE)/nuclear factor kappa-B (NF-κB) pathway-mediated neuroinflammatory response and reactive astrocyte in Parkinsonʹs disease (PD) mice

and to explore the mechanism of EA in the prevention and treatment of PD.

Methods

2

Thirty-six male C57BL/6 mice were randomly divided into a control group

a model group

and an EA group

with 12 mice in each group. The PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1

2

3

6-tetrahydropyridine (MPTP) for 7 consecutive days. From the first day of model establishment

mice in the EA group received EA at "Baihui" (GV20) and bilateral "Shenshu" (BL23)

with continuous wave

frequency of 2 Hz and intensity of 2 mA

15 min each time

once daily

for 14 days. Pole test

hanging test

and gait analysis were used to assess behavioral performance. Immunofluorescence staining was used to detect tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) positive cells in the substantia nigra of the midbrain. ELISA was used to detect α-synuclein (α-syn) content in the substantia nigra. Western blot was used to detect protein expression levels of TH

HMGB1

RAGE

NF-κB

phosphorylated NF-κB (p-NF-κB)

GFAP

tumor necrosis factor-α (TNF-α)

interleukin-6 (IL-6)

and interleukin-10 (IL-10) in the substantia nigra. Real-time quantitative PCR was used to detect mRNA expression levels of HMGB1

RAGE

NF-κB

GFAP

TNF-α

IL-6

and IL-10 in the substantia nigra.

Results

2

Compared with the control group

the model group showed prolonged pole test time (

P

<

0.01)

decreased hanging score (

P

<

0.01); shortened stride length and standing time (

P

<

0.01)

increased step frequency (

P

<

0.01)

and prolonged swing time (

P

<

0.01) of bilateral forelimbs and hindlimbs; the number of TH-positive cells and TH protein expression level

as well as IL-10 protein and mRNA expression levels in the substantia nigra were decreased (

P

<

0.01

P

<

0.05)

while α-syn content and the number of GFAP-positive cells

protein and mRNA expression levels of HMGB1

RAGE

GFAP

TNF-α

and IL-6

as well as p-NF-κB/NF-κB and NF-κB mRNA expression were increased (

P

<

0.05

P

<

0.01). Compared with the model group

the EA group showed shortened pole test time (

P

<

0.01)

increased hanging score (

P

<

0.05); increased stride length (

P

<

0.05

P

<

0.01)

decreased step frequency (

P

<

0.01)

prolonged standing time (

P

<

0.05

P

<

0.01)

and shortened swing time (

P

<

0.05) of bilateral forelimbs and hindlimbs; the number of TH-positive cells

TH protein level

and IL-10 protein and mRNA expression levels in the substantia nigra were increased (

P

<

0.01

P

<

0.05)

while α-syn content and the number of GFAP-positive cells

protein and mRNA expression levels of HMGB1

RAGE

GFAP

TNF-α

and IL-6

as well as p-NF-κB/NF-κB and NF-κB mRNA expression were decreased (

P

<

0.05

P

<

0.01).

Conclusion

2

EA can improve motor dysfunction in PD mice

protect dopaminergic (DA) neurons

and reduce α-syn protein aggregation

thereby exerting a neuroprotective effect. This effect may be related to inhibition of reactive astrocyte activation and the HMGB1/RAGE/NF-κB pathway

thereby reducing neuroinflammatory responses.