Abstract

Asthma is a heterogeneous disease, and the central nervous system (CNS) also participates in the pathogenesis of asthma. We previously reported the amygdala might regulate asthmatic attacks via projecting to the paraventricular hypothalamic nucleus (PVN). The dorsal vagal complex (DVC) is a crucial region that modulates respiratory. This study aimed to observe the activity in both PVN and DVC and the connection between PVN and DVC in asthmatic rats. Immunohistochemistry was conducted to observe the changes in Fos and oxytocin (OT) expression. Retrograde tracing using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and double immunohistochemistry for OT and Fos was used to observe the HRP/OT/Fos positive neurons distribution in the PVN. The results showed that during an asthma attack, the Fos positive neurons increased in both PVN and DVC over time. The expression of OT positive neurons in PVN showed a similar trend in parallel to the c-Fos positive neurons in PVN. The HRP retrograde-labeled neurons were densely distributed in the medial and lateral subnucleus in the PVN. OT+/HRP+ and Fos+/OT+/HRP+ accounted for 18.14%, and 2.37% of HRP-labeled neurons, respectively. Our study showed PVN and DVC were activated and the expression of OT positive neurons in PVN were increased over time during an asthma attack. The existence of connection between PVN and DVC suggested the OT neurons in PVN might project to DVC which might be involved in the pathogenesis of asthma.

Highlights

  • The pathogenesis of asthma is complex and has not yet been fully clarified

  • The asthmatic rats were subjected to 1% OVA inhalation on days 15–17 after they were sensitized to stimulate asthma attack

  • Inflammatory cell infiltration could be observed in the bronchial wall and pulmonary interstitial space in the asthmatic rats, and the proportion of eosinophils in Bronchoalveolar Lavage Fluid (BALF) increased significantly (p < 0.001) (Figures 1A,B)

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Summary

Introduction

The pathogenesis of asthma is complex and has not yet been fully clarified. Recent studies have indicated that the central nervous system (CNS) participated in the initiation of an asthma attack, especially in some patients with emotional disorders (Kline and Rose, 2014; Ritz et al, 2019a). The vagus nerve can transmit peripheral inflammatory information to the brain, which is a crucial pathway for immune-brain communication (Dantzer and Wollman, 2003; Wrona, 2006; Mazzone and Undem, 2016). Peripheral inflammatory information is transmitted to the NTS through the vagus nerve (Simonyan et al, 2012; Chen et al, 2017) and a reciprocal connection occurs between the NTS and the hypothalamus.

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