Objective

2

To observe the effects of electroacupuncture (EA) at Fengchi (GB20) and Gongxue (Extra) on the phosphatidylinostitol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapanycin (mTOR) signaling pathway and hippocampal neuronal autophagy in rats with chronic sleep deprivation (CSD)

and to explore the potential mechanisms of EA in treating CSD-related cognitive impairment.

Methods

2

A total of 65 Wistar rats with normal cognitive function were screened

and 12 were randomly selected as the control group. The remaining rats were subjected to a modified multiple-platform water environment method to induce the CSD model. Forty-eight successfully modeled rats were randomly divided into a model group

an EA group

an activator group

and an EA+activator group

with 12 rats in each group. The EA group was treated with EA at bilateral Fengchi (GB20) and Gongxue (Extra) for 20 min

once daily. The activator group was treated with intraperitoneal injection of PI3K activator 740Y-P (0.02 mg/kg) once daily. The EA+activator group was treated with EA

followed by intraperitoneal injection of 740Y-P. All interventions lasted for 14 days. Cognitive function was assessed using the Morris water maze. Golgi staining was used to observe dendritic branching and spine density in the hippocampal CA1 region. Western blot was employed to detect protein expression levels of phosphorylated PI3K (p-PI3K)

PI3K

p-AKT

AKT

p-mTOR

mTOR

microtubule-associated protein light chain 3 (LC3)Ⅱ

LC3Ⅰ

and Beclin-1 in hippocampal tissues. Immunofluorescence staining was used to detect positive expression of Beclin-1 and LC3 in the hippocampal CA1 region.

Results

2

Compared with the control group

the rats in the model group and activator group exhibited prolonged escape latency and fewer platform crossings (

P

<

0.05)

fewer dendritic branches and lower spine density in hippocampal CA1 pyramidal neurons (

P

<

0.05)

decreased positive expression of Beclin-1 and LC3 (

P

<

0.05)

increased ratios of p-PI3K/PI3K

p-AKT/AKT

and p-mTOR/mTOR (

P

<

0.05)

and decreased expression levels of LC3Ⅱ/Ⅰ and Beclin-1 (

P

<

0.05). Compared with the model group

the activator group and EA+activator group

the rats in the EA group showed shortened escape latency

increased platform crossings (

P

<

0.05)

enriched dendritic branching and higher spine density (

P

<

0.05)

increased positive expression of Beclin-1 and LC3 in the CA1 region (

P

<

0.05)

decreased ratios of p-PI3K/PI3K

p-AKT/AKT

and p-mTOR/mTOR (

P

<

0.05)

and elevated protein expression of LC3Ⅱ/Ⅰ and Beclin-1 (

P

<

0.05).

Conclusion

2

EA at Fengchi (GB20) and Gongxue (Extra) could promote dendritic spine formation

enhance synaptic plasticity

and improve cognitive function in rats with CSD. These effects may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway and activation of hippocampal neuronal autophagy.