Vagotomy Alters Astrocyte Morphology in the Brainstem Nucleus Tractus Solitarii
Authors: Hofmann Gabrielle C. , Hasser Eileen M. , Kline David D. 
Published: April 2020

The nucleus tractus solitarii (nTS) in the brainstem is the initial site of integration and modulation of sensory input from the cardiorespiratory system. The nTS is critical for maintaining blood pressure (BP), heart rate (HR), and respiratory homeostasis, and is an essential part of the reflex response to hypoxia. Alterations in both afferent input and nTS function occur in many cardiorespiratory conditions, including obstructive sleep apnea, hypertension, and heart failure. Visceral sensory information is provided to the nTS, in part, by afferents from the vagus nerves. Vagal afferents activate both neurons and astrocytes to modify nTS output and cardiorespiratory function. Vagotomy has been shown to decrease nTS neuronal activity, but whether this is a direct effect on neurons or indirect due to effects on astrocytes is unknown. We hypothesized that decreased afferent input (vagotomy) modifies nTS astrocyte morphology, and is associated with impaired cardiorespiratory responses to hypoxia. To test this hypothesis, male Sprague‐Dawley rats (5–7 weeks old) underwent either right cervical vagotomy caudal to the nodose (n=8), sham surgery (n=7), or no surgery/control (n=4). Prior to surgery and one week post‐surgery, cardiorespiratory parameters (respiration, oxygen saturation, HR, BP) were measured in conscious and anesthetized animals under baseline and hypoxic conditions (8–12% O2). Rats were euthanized and brains were examined across the caudal‐to‐rostral nTS. Immunohistochemistry was used to evaluate astrocytes with glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B), and glutamatergic synapses with vesicular glutamate transporter 2 (VGLUT2) in the nTS. Immunoreactivity (‐IR) was compared between the left (intact) and right (manipulated) nTS among groups. Vagotomy increased astrocytic GFAP‐IR compared to sham and controls in both the intact and manipulated sides, primarily at the level of the area postrema. Sholl analysis of astrocyte processes showed that vagotomy increased the number of astrocyte branch segments and branchpoints compared to controls on the manipulated side, and both vagotomy and sham increased branching on the manipulated side compared to controls. The latter occurred at unique proximal and distal distances from the cell body. The number of S100B‐IR astrocytes increased in vagotomy (compared to sham) in the intact side, with a trend in the manipulated side. VGLUT2‐IR was not different among groups or between sides, suggesting a similar number of glutamate synapses and lack of their pruning with vagotomy. Cardiorespiratory responses to hypoxia were not altered after vagotomy. These data suggest decreased afferent input increases astrocyte number and morphology, which is likely due to reduced afferent activity rather than presynaptic afferent structural alterations. Thus, afferent input dynamically influences astrocyte structure and likely function to modify neuronal activity, further elucidating the importance of nTS astrocytes in cardiorespiratory homeostasis and disease.

Support or Funding Information

T32 OD011126, R01 HL132836, R01 HL128454