Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke

  • Zhifu Wang
  • Bingbing Lin
  • Weilin Liu
  • Hongwei Peng
  • Changming Song
  • Jia Huang
  • Zuanfang Li
  • Lidian Chen
  • Jing TaoEmail author
Original Article


Hippocampal 5-HT1A receptors and the PKA signaling pathway have been implicated in learning and memory. This study aimed to investigate whether PKA signaling mediated by 5-HT1A receptors was involved in the electroacupuncture (EA)-mediated learning and memory in a rat model of middle cerebral artery occlusion-induced cognitive deficit (MICD). Compared to no treatment or non-acupoint EA treatment, EA at DU20 and DU24 acupoints improved the neurological deficit of scores, shortened escape latency and increased the frequency of crossing the platform in the Morris water maze test. T2-weighted imaging demonstrated that the MICD rat brain lesions were mainly located in the cortex and hippocampus, and injured volumes were reduced after EA. Furthermore, we found that these behavioral changes were concomitant with the deficit of the 5HT1A and PKA signaling pathways in the hippocampus, as the activation of the 5-HT1A receptor, the reduction of PKA kinase activity, and AMPA and NMDA receptor phosphorylation occurred in the injured hippocampus at Day 14 after MICD. Additionally, EA dramatically elevated the activation of PKA. Moreover, EA significantly increased intracellular calcium concentrations regulated by the activation of NMDA receptors. Therefore, PKA kinase and NMDA receptors mediated by 5-HT1A receptors in the hippocampus might contribute to improving learning and memory during the recovery process following ischemic stroke with an EA intervention.


Middle cerebral artery occlusion-induced cognitive deficit (MICD) Electroacupuncture Protein kinase a (PKA) 5-HT1A receptor Memory 



The present study was supported by the Natural Science Foundation of China (NO.81403450) and the Natural Science Foundation of Fujian Province (NO.2016 J01382) and the Foundation of Collaborative Innovation Center of Rehabilitation Technology (Fujian Province) (NO.2016001-collaborative).

Authors’ contributions

Zhifu Wang and Bingbing Lin contributed equally to this work.

Compliance with ethical standards

Conflict of interest

The authors declare no financial or commercial conflicts of interest.

Supplementary material

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ESM 1 (DOC 31 kb)
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Neuronal damage in the ischemic brain areas of MICD model rats. (A-O) showed the representative images and quantitative graphs for immunostaining with NeuN (brown cell) antibody on different brain areas of sham and MICD groups at 14 days. (A-G) present the NeuN immunostaining of the MICD group in ischemic (B-D) cortex and (E-G) CA1. (H-N) present the NeuN immunostaining of the sham group in ipsilateral (I-K) cortex and (L-N) CA1. (A)(H) Original magnification ×25. (B)(E)(I)(L) Original magnification ×100. (C)(F)(J)(M) Original magnification ×200. (D)(G)(K)(N) Original magnification ×400. Values are expressed as the means±SEM (n = 6 for each group). **P < 0.01. MICD: middle artery occlusion-induced cognitive deficit. (PNG 15 kb)

11011_2019_489_MOESM2_ESM.tif (39 kb)
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhifu Wang
    • 1
  • Bingbing Lin
    • 1
  • Weilin Liu
    • 1
  • Hongwei Peng
    • 1
  • Changming Song
    • 1
  • Jia Huang
    • 1
  • Zuanfang Li
    • 1
  • Lidian Chen
    • 1
  • Jing Tao
    • 1
    Email author
  1. 1.Fujian University of Traditional Chinese MedicineFuzhouChina

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