Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment
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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.
KeywordsCID Diabetic rat Glutamate receptors Hippocampus Neuronal apoptosis
Cognitive impairment in diabetes
Glutamate (glutamic acid)
Metabotropic glutamate receptors
Ionotropic glutamate receptor
NMDA glutamate receptor
NMDAR subunits 1
NMDAR subunits 2A
NMDAR subunits 2B
AMPA glutamate receptor
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.
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
The authors declare that they have no competing interests.
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