Peripheral vagus nerve stimulation significantly affects lipid composition and protein secondary structure within dopamine-related brain regions in rats

Abstract

Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders.

Fig. 1

Visual images of unstained sections of rat brain showing the loci of the areas analyzed using the FTIRMS technique; a CX—motor cortex, STR—striatum, the medial part of caudate putamen; NAC—nucleus accumbens; b VTA—ventral tegmental area, SN—substantia nigra; c DMV—dorsal motor nucleus of the vagus nerve. Scale bars 1 mm

Fig. 2

Second-derivative FTIRMS spectra of: a lipid massive; b Amide I–II spectral range (seven-point Savitzky–Golay filtration was applied to produce decent-looking spectra). For the sake of clarity, the second derivative was multiplied by −1

Fig. 3

a FTIRMS map of STR; b typical FTIRMS spectrum of STR, extracted from FTIRMS map; curve fitting of the FTIRMS spectrum for: c lipid massive; d Amide I

Fig. 4

Exemplar FTIRMS images presenting 2D distribution of selected parameters within brain regions analyzed for a stimulated animal;  %ALPHA according to Eq. 2.2; UNSAT according to Eq. 1.1; lipid/protein according to Eq. 1.3

Fig. 5

Comparison of changes in lipid composition between the microchip-stimulated group (MC) and the control (C): a total fatty acyl chain absorptions; b the FACL; c the level of lipid unsaturation. R—right hemisphere; L—left hemisphere. Assignments: upward arrow a statistically significant (p < 0.05) increase was observed in both hemispheres; downward arrows a statistically significant (p < 0.05) decrease was observed in both hemispheres; black spade suit asymmetric change (p < 0.05) occurred in both hemispheres (i.e., a decrease in the first one and an increase in the second one); asterisk a statistically significant change (p < 0.05) in a specific parameter was observed in one hemisphere

Fig. 6

Comparison of changes in protein composition between the microchip-stimulated group (MC) and the control (C): a the percentage content of alpha helices; b percentage content of beta sheets; c percentage content of beta turns; percentage content of random coils; e integrated area of Amide I. R—right hemisphere; L—left hemisphere. Assignments: upward arrow a statistically significant (p < 0.05) increase was observed in both hemispheres; downward arrow a statistically significant (p < 0.05) decrease was observed in both hemispheres; black spade suit asymmetric change (p < 0.05) occurred in both hemispheres (i.e., a decrease in the first one and an increase in the second one); asterisk a statistically significant change (p < 0.05) in a specific parameter was observed in one hemisphere

Fig. 7

Comparison of changes in the lipid-to-protein ratio between the microchip-stimulated group (MC) and the control (C). R—right hemisphere; L—left hemisphere

Fig. 8

Global spectral changes in lipid massive for: a the dorsal motor nucleus of the vagus nerve (DMV); b the ventral tegmental area (VTA); c the substantia nigra SN; d the nucleus accumbens (NAC); e the corpus striatum spaces (STR_E); f the fiber bundles of striatum (STR_F); g the motor cortex (CX). CR—control group, right hemisphere; CL—control group, left hemisphere; MCR—microchip-stimulated group, right hemisphere; MCL—microchip-stimulated group, left hemisphere

Fig. 9

Global spectral changes in Amide I for: a dorsal motor nucleus of the vagus nerve (DMV); b ventral tegmental area (VTA); c substantia nigra (SN); d nucleus accumbens (NAC); e corpus striatum spaces (STR_E); f fiber bundles of striatum (STR_F); g motor cortex (CX). CR—control group, right hemisphere; CL—control group, left hemisphere; MCR—microchip-stimulated group, right hemisphere; MCL—microchip-stimulated group, left hemisphere