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Research Paper|Volume 12, Issue 10|pp 8923—8938

Influence of human amylin on the membrane stability of rat primary hippocampal neurons

Nan Zhang1,2, Yuan Xing3,4, Yongzhou Yu5, Chao Liu6, Baohua Jin5, Lifang Huo5, Dezhi Kong5, Zuxiao Yang5, Xiangjian Zhang7, Ruimao Zheng8, Zhanfeng Jia9, Lin Kang10, Wei Zhang5
  • 1Central Laboratory, First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • 2Hebei International Joint Research Center for Brain Science, Shijiazhuang, Hebei, China
  • 3Department of Neurology, First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • 4Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei, China
  • 5Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, Hebei, China
  • 6Department of Laboratory Animal Science, Hebei Medical University, Hebei Key Lab of Laboratory Animal Science, Shijiazhuang, Hebei, China
  • 7Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • 8Department of Anatomy, Histology and Embryology, Health Science Center, Neuroscience Research Institute, Key Laboratory for Neuroscience of the Ministry of Education, Key Laboratory for Neuroscience of the National Health Commission, Peking University, Beijing, China
  • 9Department of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Center for Innovative Drug Research and Evaluation, Institute of Medical Science and Health, The Key Laboratory of Neural and Vascular Biology Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei, China
  • 10Department of Endocrinology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Clinical Medical Research Center, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
Received: November 8, 2019Accepted: March 9, 2020Published: May 28, 2020
https://doi.org/10.18632/aging.103105

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The two most common aging-related diseases, Alzheimer’s disease and type 2 diabetes mellitus, are associated with accumulation of amyloid proteins (β-amyloid and amylin, respectively). This amylin aggregation is reportedly cytotoxic to neurons. We found that aggregation of human amylin (hAmylin) induced neuronal apoptosis without obvious microglial infiltration in vivo. High concentrations of hAmylin irreversibly aggregated on the surface of the neuronal plasma membrane. Long-term incubation with hAmylin induced morphological changes in neurons. Moreover, hAmylin permeabilized the neuronal membrane within 1 min in a manner similar to Triton X-100, allowing impermeable fluorescent antibodies to enter the neurons and stain intracellular antigens. hAmylin also permeabilized the cell membrane of astrocytes, though more slowly. Under scanning electron microscopy, we observed that hAmylin destroyed the integrity of the cell membranes of both neurons and astrocytes. Additionally, it increased intracellular reactive oxygen species generation and reduced the mitochondrial membrane potential. Thus, by aggregating on the surface of neurons, hAmylin impaired the cell membrane integrity, induced reactive oxygen species production, reduced the mitochondrial membrane potential, and ultimately induced neuronal apoptosis.