Neurochemical Research

, Volume 44, Issue 4, pp 978–993 | Cite as

Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment

  • Xiao-Peng Wang
  • Pin Ye
  • Jiao Lv
  • Lei Zhou
  • Zhong-Yi Qian
  • Yong-Jie Huang
  • Zhi-Hao Mu
  • Xie Wang
  • Xin-jie Liu
  • Qi Wan
  • Zhi-Hong YangEmail author
  • Fang WangEmail author
  • Ying-Ying ZouEmail author
Original Paper


Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-d-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.


CID Diabetic rat Glutamate receptors Hippocampus Neuronal apoptosis 



Cognitive impairment in diabetes


Glutamate (glutamic acid)


Glu receptor


Metabotropic glutamate receptors


Ionotropic glutamate receptor




NMDA glutamate receptor


NMDAR subunits 1


NMDAR subunits 2A


NMDAR subunits 2B


α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


AMPA glutamate receptor


Diabetes mellitus


Long-term potentiation


Long-term depression






Alzheimer’s disease



This study was supported in part by grants (81760149, 81360176, 81200840 and 81260361) from the National Natural Sciences Foundation of China, a grant (2013HB078) from the Department of Science and Technology of Yunnan Province, the grants (2017FE468 (-171) and 2017FE468) from the Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University, and the grant (2018JS156) from Yunnan provincial Education Commission.

Author’s Contributions

YYZ is the corresponding author, FW and ZHY are the co-corresponding author of this article. XPW, PY and JL contributed equally to this work. YYZ, FW and ZHY designed the project, contributed to the analysis of data and finalization of the manuscript. XPW conducted most of the experiments. PY conducted part of experiments and prepared the first draft of the manuscript. JL conducted part of experiments and participated in editing the manuscript. LZ guided the Morris Water Maze testing and analysis of data. ZYQ carried out the paraffin embedding, sectioning, H&E and immunofluorescence staining. YJH helped with removal of tissue samples and took care of the experimental rats. QW revised the manuscript. ZHM, XJL and XW carried out part of analysis of data and editing the manuscript, QW revised the manuscript. All authors have read and approved the final version of the manuscript.

Compliance with Ethical Standards

Competing interests

The authors declare that they have no competing interests.


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Copyright information

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

Authors and Affiliations

  • Xiao-Peng Wang
    • 1
    • 6
  • Pin Ye
    • 2
  • Jiao Lv
    • 1
  • Lei Zhou
    • 3
  • Zhong-Yi Qian
    • 4
  • Yong-Jie Huang
    • 1
    • 7
  • Zhi-Hao Mu
    • 1
  • Xie Wang
    • 1
  • Xin-jie Liu
    • 1
    • 8
  • Qi Wan
    • 5
  • Zhi-Hong Yang
    • 1
    Email author
  • Fang Wang
    • 1
    Email author
  • Ying-Ying Zou
    • 1
    Email author
  1. 1.Department of Pathology and Pathophysiology, Faculty of Basic Medical SciencesKunming Medical UniversityKunmingPeople’s Republic of China
  2. 2.Department of Human Anatomy and Histology/Embryology, Faculty of Basic Medical SciencesKunming Medical UniversityKunmingPeople’s Republic of China
  3. 3.The Key Laboratory of Stem Cell and Regenerative Medicine of Yunnan ProvinceKunming Medical UniversityKunmingPeople’s Republic of China
  4. 4.Department of Morphological Laboratory, Faculty of Basic Medical SciencesKunming Medical UniversityKunmingPeople’s Republic of China
  5. 5.Institute of Neuroregeneration & Neurorehabilitation, Department of Neurosurgery of the Affiliated HospitalQingdao UniversityQingdaoPeople’s Republic of China
  6. 6.Drug Rehabilitation CenterDatongPeople’s Republic of China
  7. 7.Emergency DepartmentFirst Affiliated Hospital of KunmingKunmingPeople’s Republic of China
  8. 8.Undergraduate of Batch 2016 in Clinical Medicine Major, Faculty of Basic Medical SciencesKunming Medical UniversityKunmingPeople’s Republic of China

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