Objective To observe the effect of electroacupuncture(EA) on the expressions of tight junction related proteins Claudin-5

ZO-1 in the colon and hippocampus

Toll-like receptor 4/nuclear factor-kappa B/NOD-like receptor protein 3(TLR4/NF-κB/NLRP3) pathway in the hippocampus of APP/PS1 mice

so as to explore its mechanisms underlying improvement of cognitive impairment. Methods Eighteen 5-month-old male APP/PS1 mice were equally randomized into model and EA groups

and nine 5-month-old male C57 BL/6 mice were used as the normal control. EA(2 Hz

1 mA) was applied to “Baihui”(GV20)

“Dachangshu”(BL25) and “Zusanli”(ST36) for 15 min

once daily

5 days a week for 5 weeks. The Morris water maze swimming test was used to evaluate the mice's cognitive impairment. Nissl staining was used to observe the pathological morphology of hippocampus. The expression of amyloid β-peptide(Aβ) in brain tissue was detect by immunohistochemistry; the contents of lipopolysaccharide(LPS) in colon

serum and hippocampus were detected by ELISA; the expression levels of Claudin-5

ZO-1 in colon and hippocampus

and TLR4/NF-κB/NLRP3 pathway related proteins in hippocampus were detected by Western blot. Results Compared with the normal group

the escape latency of the mice in the model group was prolonged from the 3

(rd)

day(P

<

0.05

P

<

0.01)

the number of crossing the platform and the percentage of target quadrant residence time were significantly decreased(P

<

0.01)

and the contents of LPS in colon

serum and hippocampus were significantly increased(P

<

0.01)

the expression levels of TLR4

NF-κB p65

NLRP3

Caspase-1

interleukin(IL)-1β and tumor necrosis factor(TNF)-α in hippocampus and Aβ in brain tissue were significantly increased(P

<

0.01)

while the expression levels of Claudin-5

ZO-1 in colon and hippocampus were significantly decreased(P

<

0.01). Compared with the model group

the escape latency of mice in the EA group was shortened from the 4(rd) day(P

<

0.05

P

<

0.01)

the number of crossing the platform and the percentage of target quadrant residence time were significantly decreased(P

<

0.01)

and the contents of LPS in colon

serum and hippocampus were significantly increased(P

<

0.01)

the expression levels of TLR4

NF-κB p65

NLRP3

Caspase-1

interleukin(IL)-1β and tumor necrosis factor(TNF)-α in hippocampus and Aβ in brain tissue were significantly increased(P

<

0.01)

while the expression levels of Claudin-5

ZO-1 in colon and hippocampus were significantly decreased(P

<

0.01). Compared with the model group

the escape latency of mice in the EA group was shortened from the 4

(th)

day(P

<

0.05

P

<

0.01)

the number of crossing the platform and the percentage of target quadrant residence time were increased(P

<

0.01

P

<

0.05)

and the contents of LPS in serum and hippocampus were decreased(P

<

0.05)

and the expression levels of TLR4

NF-κB p65

Caspase-1

NLRP3

IL-1β

TNF-α in hippocampus and Aβ in brain tissue were significantly decreased(P

<

0.05

P

<

0.01)

while the expression levels of Claudin-5

ZO-1 in colon and hippocampus were significantly increased(P

<

0.05

P

<

0.01). Outcomes of Nissl staining showed dispersed arrangement of neurons with nuclear pyknosis or hyperchromasia in the hippocampus

and a decreased number of cell layers in the model group

which was relatively milder in the EA group. Conclusion EA may improve the cognitive impairment of APP/PS1 mice by up-regulating the expression of Claudin-5 and ZO-1

reducing the transposition of gut-derived LPS to the central nervous system

inhibiting the over-activation of TLR4/NF-κB/NLRP3 pathway

and alleviating the inflammatory reaction of the central nervous system.