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

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.

Neuronal Inflammation is Associated with Changes in Epidermal Innervation in High Fat Fed Mice

“…Previous studies indicate nondiabetic rodents fed a high fat diet develop obesity (Obrosova et al, 2007;Watcho et al, 2010;Jaroslawska et al, 2021), dyslipidemia (Vincent et al, 2009;Guilford et al, 2011;Ozay et al, 2014;Zhang et al, 2018;Jaroslawska et al, 2021), and signs of PN including morphological changes in peripheral nerves (Zhang et al, 2018), reduced sensory and motor nerve conduction velocities (Vincent et al, 2009;Xu et al, 2014), altered thermal sensitivity (Obrosova et al, 2007;Guilford et al, 2011;Xu et al, 2014;Zhang et al, 2018), and mechanical hypersensitivity (Guilford et al, 2011;Xie et al, 2013;Zhang et al, 2018). However, the distinct mechanisms underlying high fat diet-induced PN have yet to be elucidated.…”

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

“…Damage to the vasa nervorum, which supply various nerve fibers, such as C-type and delta fibers responsible for specific functions of the nervous system, is mainly responsible for impaired wound healing in DM and its recurrence, especially in DFS [ 26 ]. This highlights the importance of imitating neuropathic changes in the design of the animal model [ 27 ]. Impaired microcirculation in the skin in patients with DM occurs due to damage to the vasa nervorum caused by thickening of the basal membrane of those arteries and their persistent occlusion by microclots.…”

The receptor for advanced glycation end products and its ligands’ expression in OVE26 diabetic sciatic nerve during the development of length‐dependent neuropathy

“…Until now, evidence indicated that a variety of factors, such as local neuroinflammation, malfunctions in cytoskeleton remodeling, impaired axonal transport, and enhanced oxidative stress, might be involved in the progression of LDN in patients suffering from diabetes. [6][7][8][9][10][11] Advanced glycation end products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids. AGEs may accumulate in different biological locations, such as the peripheral nervous system (PNS).…”