Effect of long term-administration of aspartame on the ultrastructure of sciatic nerve

Abstract

Aspartame is the most widely used artificial sweetener worldwide. There is much controversy about the effect of aspartame on different cells in the body. The aim of this study was to evaluate the effect of aspartame on the structure of the sciatic nerve. Thirty adult male albino rats were divided into three groups. Group I served as control; Group II received aspartame orally in a dose of 250 mg/kg/d for 3 months; Group III received aspartame at the same dose and for the same period, and was allowed to recover for 1 month. Specimens of sciatic nerve were processed, and semithin and ultrathin sections were examined by light and electron microscopy. A morphometric study was done to evaluate the g-ratio, which is the ratio between the axon diameter and total fiber diameter. Long-term aspartame administration resulted in many degenerative changes affecting mainly the myelin sheath, in the form of focal and extensive demyelination; disruption and splitting of myelin lamellae with loss of compact lamellar structure; and excessive enfolding with irregular thickening of myelin sheaths. Less frequent than those observed in the myelin sheath, some axonal changes were detected, such as compression and distortion. Dilated rough endoplasmic reticulum and vacuolation of the cytoplasm of Schwann cells were also detected. Partial improvement was observed in the recovery group. It was concluded that long-term administration of aspartame had a harmful effect on the structure of sciatic nerve and 1 month stoppage of aspartame was not enough to achieve complete recovery.

Keywords: Aspartame; Sciatic nerve; Ultrastructure.

Figure 1

Photomicrographs of toluidine-blue-stained semithin sections of rat sciatic nerve. (A, B) Control Group showing myelinated nerve fibers of various sizes with end oneurium (E) in between. (C–G) Aspartame Group showing (C) increased spaces (star) in between nerve fibers, (D–F) dilated blood vessel (arrow) containing many cells with irregular nuclei, (E) multiple myelin loops (arrow heads) and focal lysis of myelin sheath (biffed arrow) of some fibers, (F) excess demyelination and degeneration of myelin sheath (double arrow) in other fibers, and (G) irregular myelin thickening (waved arrow) in many nerve fibers. (H) Recovery Group showing nearly normal myelinated nerve fibers, Schwann cells (curved arrow) and endoneurium (E) in control group with some focal lysis (biffed arrow). Toluidine blue, 1000×.

Fig. 2

Electron micrographs of ultrathin sections of rat sciatic nerve of the (A, B) Control Group showing, normal myelinated (mn) and unmyelinated (un) nerve fibers, and axoplasm (Ax) of myelinated fibers containing multiple microtubules and mitochondria (M), that are wrapped in a thick myelin sheath with compact lamellar structure and surrounded by Schwann cells (Sch). (C–H) Aspartame Group showing blood vessels (arrow) lined by endothelial cells and containing (C, D) monocytes with irregular nuclei (curved arrow), (E) focal lysis (biffed arrow) of myelin sheath with (E, F) appearance of redundant myelin (double arrow) and (G, H) formation of myelin loop (arrow head).

Fig. 3

Electron micrographs of ultrathin sections of rat sciatic nerve of Aspartame Group showing (A) separation (incisures) of myelin lamellae (arrow) with (B) focal loss of compact lamellar structure (splitting) of myelin sheath (double arrow), (C) discontinuous and disorganized myelin sheath (biffed arrow) with (D) marked lysis (star), (E, F) abnormal and irregular thickening of myelin (waved arrow), with compressed distorted axoplasm (Ax), (G, H) Schwann cells (Sch) with swollen and destroyed mitochondria (M), dilated rough endoplasmic reticulum (R), and vacuolation (V) of the cytoplasm.

Fig. 4

Electron micrographs of ultrathin sections of rat sciatic nerve of the Recovery Group showing (A, B) multiple axons (Ax) with normal appearance and endoneurium (E) in between, surrounded by myelin sheath and Schwann cells (Sch), with (C–E) some focal lysis (biffed arrow), (D) focal appearance of redundant myelin (double arrow), and (E, F) membrane-bound vacuoles (V) in some axons (Ax) with (G, H) separation (arrow) of myelin sheath from the axon at some sites.

Fig. 5

Histogram showing the mean value of the axon/fiber (A/F) ratio (g-ratio) in the sciatic nerve of different groups. * p <0.0001 is highly significant versus control group. ASP = aspartame.