Peripheral Neuropathy Presents Similar Symptoms and Pathological Changes in Both High-Fat Diet and Pharmacologically Induced Pre- and Diabetic Mouse Models.

Julia Jaroslawska,Krzysztof Wasowicz,Judyta K Juranek,Joanna Wojtkiewicz,Kamila Zglejc-Waszak,Tomasz Antonowski,Agnieszka Korytko,Andrzej S Pomianowski

doi:10.3390/life11111267

Julia Jaroslawska, Krzysztof Wasowicz + Show 6 more

Open Access

https://doi.org/10.3390/life11111267

Copy DOI

Journal: Life	Publication Date: Nov 19, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: University of Warmia and Mazury in Olsztyn

Abstract

The objective of the study was to compare the effects of experimentally induced type 1 or type 2 diabetes (T1D or T2D) on the functional, structural and biochemical properties of mouse peripheral nerves. Eight-week-old C57BL/6 mice were randomly assigned into three groups, including the control (CTRL, chow-fed), STZ (streptozotocin (STZ)-injected), and HFD (high-fat diet (HFD)-fed) group. After 18-weeks of experimental treatment, HFD mice had higher body weights and elevated levels of plasma lipids, while STZ mice developed hyperglycemia. STZ-treated mice, after an extended period of untreated diabetes, developed motor and sensory nerve conduction-velocity deficits. Moreover, relative to control fibers, pre- and diabetic axons were lower in number and irregular in shape. Animals from both treatment groups manifested a pronounced overexpression of nNOS and a reduced expression of SOD1 proteins in the sciatic nerve, indicating oxidative–nitrosative stress and ineffective antioxidant protection in the peripheral nervous system of these mice. Collectively, STZ- and HFD-treated mice revealed similar characteristics of peripheral nerve damage, including a number of morphological and electrophysiological pathologies in the sciatic nerve. While hyperglycemia is a large component of diabetic neuropathy pathogenesis, the non-hyperglycemic effects of diabetes, including dyslipidemia, may also be of importance in the development of this condition.

Highlights

Diabetic peripheral neuropathy (DPN) affects nearly 50% of adults with diabetes, which makes it one of the most common complications of this condition [1]
The mechanism underlying neuropathy in diabetes remains unknown, but it has been established that RAGE might play a role in its pathogenesis [3]
As compared to CTRL, motor NCV (MNCV) values were significantly decreased in STZ mice, both at 2 (36.86 ± 1.97 vs. 29.22 ± 1.95 m/s, respectively, p < 0.05) and 4.5 (36.15 ± 2.49 vs. 25.63 ± 2.45 m/s, respectively, p < 0.01) months after STZ administration (Figure 2A)

Summary

Introduction

Diabetic peripheral neuropathy (DPN) affects nearly 50% of adults with diabetes, which makes it one of the most common complications of this condition [1]. DPN is a neurodegenerative disorder that preferentially targets sensory and autonomic axons, subsequently damaging motor nerve terminals, the latter are most often affected to a lesser degree [2]. The disorder leads to a loss of a sensory function resulting in so-called neuropathic pain and is associated with substantial morbidity. Peripheral nerves are the most susceptible tissues to pathological changes due to hyperglycemia. It has been speculated that long-term hyperglycemia could cause RAGE-related inflammation and oxidative stress. RAGE, by its binding to proinflammatory ligands such as high-mobility group protein (B) (HMGB1) and S100B, causes the activation of nuclear transcription factors such as NF-κB, STAT and JKN [3]. RAGE can contribute to the progress of several neurodegenerative diseases: Parkinson’s, Huntington’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) [3]

Objectives

Methods

Results