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Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy

  • Tieying Song EMAIL logo , Jianhui Zhao , Xiaojing Ma , Zaiwang Zhang , Bo Jiang and Yunliang Yang
Published/Copyright: May 19, 2017
Biological Chemistry
From the journal Biological Chemistry Volume 398 Issue 10

Abstract

The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R−/− mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R−/− mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R−/− mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord.

Keywords: high fat diet; NMDA receptor; obesity; peripheral neuropathy; sigma-1 receptor

  1. Conflict of interest statement: The authors have no conflict of interest to disclose.

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Received: 2017-2-21
Accepted: 2017-4-27
Published Online: 2017-5-19
Published in Print: 2017-9-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2017-0117
Keywords for this article
high fat diet; NMDA receptor; obesity; peripheral neuropathy; sigma-1 receptor

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities
  4. Targeting and inactivation of bacterial toxins by human defensins
  5. S100A6 – focus on recent developments
  6. Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach
  7. Research Articles/Short Communications
  8. Protein Structure and Function
  9. I36T↑T mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions
  10. Cell Biology and Signaling
  11. Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells
  12. Galanin suppresses proliferation of human U251 and T98G glioma cells via its subtype 1 receptor
  13. Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy
  14. Proteolysis
  15. Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer
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