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

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Abstract

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Fujian University of Traditional Chinese Medicine, Fuzhou, China

    Zhifu Wang, Bingbing Lin, Weilin Liu, Hongwei Peng, Changming Song, Jia Huang, Zuanfang Li, Lidian Chen & Jing Tao

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  1. Zhifu Wang
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  2. Bingbing Lin
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  3. Weilin Liu
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  4. Hongwei Peng
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  8. Lidian Chen
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  9. Jing Tao
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Zhifu Wang and Bingbing Lin contributed equally to this work.

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Correspondence to Jing Tao.

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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)

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Wang, Z., Lin, B., Liu, W. et al. Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke. Metab Brain Dis 35, 549–558 (2020). https://doi.org/10.1007/s11011-019-00489-y

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