Unilateral vagotomy alters astrocyte and microglial morphology in the nucleus tractus solitarii of the rat

Abstract

The nucleus tractus solitarii (nTS) is the initial site of integration of sensory information from the cardiorespiratory system and contributes to reflex responses to hypoxia. Afferent fibers of the bilateral vagus nerves carry input from the heart, lungs, and other organs to the nTS where it is processed and modulated. Vagal afferents and nTS neurons are integrally associated with astrocytes and microglia which contribute to neuronal activity and influence cardiorespiratory control. We hypothesized that vagotomy would alter glial morphology and cardiorespiratory responses to hypoxia. Unilateral vagotomy (or sham surgery) was performed in rats. Prior to and seven days after surgery, baseline and hypoxic cardiorespiratory responses were monitored in conscious and anesthetized animals. The brainstem was sectioned and caudal, mid-area postrema (mid-AP), and rostral sections of the nTS were prepared for immunohistochemistry. Vagotomy increased immunoreactivity (-IR) of astrocytic glial fibrillary acidic protein (GFAP), specifically at mid-AP in the nTS. Similar results were found in the dorsal motor nucleus of the vagus (DMX). Vagotomy did not alter nTS astrocyte number, yet increased astrocyte branching and altered morphology. Additionally, vagotomy both increased nTS microglia number and produced morphologic changes indicative of activation. Cardiorespiratory baseline parameters and hypoxic responses remained largely unchanged, but vagotomized animals displayed fewer augmented breaths (sighs) in response to hypoxia. Altogether, vagotomy alters nTS glial morphology, indicative of functional changes in astrocytes and microglia that may affect cardiorespiratory function in health and disease.

The ins and outs of the caudal nucleus of the solitary tract: An overview of cellular populations and anatomical connections

“…In addition to neurons, astrocytes contribute heavily to the function of the cNTS. 5 Based on immunolabelling for glial-fibrillary protein (GFAP), astrocytes appear to be more densely packed in the rat NTS 82,83 than in the mouse NTS, 76,84 although, to this author's knowledge, a direct, quantitative comparison has not been made. Of note, in both species, the densest expression of GFAP is found in the border region between the AP and the cNTS, [83][84][85] where astrocytes may regulate transport of molecules across the border and thus modulate the flow of information from the blood into the NTS.…”

“…5 Based on immunolabelling for glial-fibrillary protein (GFAP), astrocytes appear to be more densely packed in the rat NTS 82,83 than in the mouse NTS, 76,84 although, to this author's knowledge, a direct, quantitative comparison has not been made. Of note, in both species, the densest expression of GFAP is found in the border region between the AP and the cNTS, [83][84][85] where astrocytes may regulate transport of molecules across the border and thus modulate the flow of information from the blood into the NTS. 81,85 In addition to forming a selectively permeable diffusion barrier between the AP and the NTS, astrocytes in the rat NTS form part of tripartite synapses, specialized synaptic arrangements consisting of a synaptic cleft containing the pre-and postsynaptic terminals covered by astrocytic processes.…”

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

“…Interestingly, astrocyte processes contacted 58% of the perimeter of NTS single synapses, and glial coverage averaged 50% in multisynaptic arrangements [25]. Furthermore, changes in astrocyte coverage within the NTS and DMNX have been observed in a variety of models, including vagotomy [26], hypoxia [27], diesel exhaust particle exposure [28], and ozone inhalation [29]. Interestingly, NTS astrocytes were also shown to respond to changes in energy status [30].…”

“…Interestingly, the DVC microglial population has been shown to respond to stimuli and lesions. Vagotomy increases NTS microglial cell numbers and produces morphological changes indicative of microglia activation [26]. Furthermore, microgliosis, comprising an increase in the number of microglial cells and a decrease in microglial branching, was observed in the NTS after short-term HFD consumption (4 days; [44]).…”

Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites

“…Vagus nerve stimulation (through non-invasive electrical current) in animal models of AD results in morphological (e.g., number of branches, branch length) changes in microglia-specifically, it induces a change from a neuro-destructive to a neuroprotective phenotype (Kaczmarczyk et al, 2018). Vagotomy alters microglia (and astrocyte) morphology (Hofmann et al, 2021). Additionally, vagus nerve ablation in mice is sufficient to prevent Lactobacillus rhamnosus-induced changes in rodent behavior (Bravo et al, 2011).…”