SEPT9 Upregulation in Satellite Glial Cells Associated with Diabetic Polyneuropathy in a Type 2 Diabetes-like Rat Model

Int J Mol Sci. 2022 Aug 19;23(16):9372. doi: 10.3390/ijms23169372.

Abstract

Despite the worldwide prevalence and severe complications of type 2 diabetes mellitus (T2DM), the pathophysiological mechanisms underlying the development of diabetic polyneuropathy (DPN) are poorly understood. Beyond strict control of glucose levels, clinical trials for reversing DPN have largely failed. Therefore, understanding the pathophysiological and molecular mechanisms underlying DPN is crucial. Accordingly, this study explored biochemical and neuropathological deficits in a rat model of T2DM induced through high-fat diet (HFD) feeding along with two low-dose streptozotocin (STZ) injections; the deficits were explored through serum lipid, neurobehavioral, neurophysiology, neuropathology, and immunohistochemistry examinations. Our HFD/STZ protocol induced (1) mechanical hyperalgesia and depression-like behaviors, (2) loss of intraepidermal nerve fibers (IENFs) and reduced axonal diameters in sural nerves, and (3) decreased compound muscle action potential. In addition to hyperglycemia, which was correlated with the degree of mechanical hyperalgesia and loss of IENFs, we observed that hypertriglyceridemia was the most dominant deficit in the lipid profiles of the diabetic rats. In particular, SEPT9, the fourth component of the cytoskeleton, increased in the satellite glial cells (SGCs) of the dorsal root ganglia (DRG) in the T2DM-like rats. The number of SEPT9(+) SGCs/DRG was correlated with serum glucose levels and mechanical thresholds. Our findings indicate the putative molecular mechanism underlying DPN, which presumably involves the interaction of SGCs and DRG neurons; nevertheless, further functional research is warranted to clarify the role of SEPT9 in DPN.

Keywords: diabetic polyneuropathy; hypertriglyceridemia; neuropathic pain; satellite glial cell; septin-9.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetes Mellitus, Type 2* / pathology
  • Diabetic Neuropathies* / pathology
  • Ganglia, Spinal / pathology
  • Glucose / therapeutic use
  • Hyperalgesia
  • Lipids / therapeutic use
  • Neuralgia* / pathology
  • Neuroglia / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Septins* / genetics
  • Streptozocin
  • Up-Regulation

Substances

  • Glucose
  • Lipids
  • Septin9 protein, rat
  • Septins
  • Streptozocin

Grants and funding

This research was funded by (1) the Ministry of Science and Technology, grant number 111-2320-B-037-010-MY3 and 111-2314-B-037-001- to Yu-Lin Hsieh; grant number 110-2320-B-214-002 to Hung-Wei Kan; grant number 108-2320-B-214-011-MY3 and 111-2320-B-214-002-MY3 to Yu-Cheng Ho; and (2) I-Shou University, grant number ISU 110-S-03 to Hung-Wei Kan.