Birth Defects Research | 2021
Introduction to the special focus on the development of the autonomic nervous system
Abstract
The autonomic nervous system (ANS) is a control system that, as the name implies, acts largely autonomously to regulate a variety of bodily functions, including breathing, digestion, heart rate and contraction, sweating, and pupillary, sexual and vascular responses (Figure 1). The coordination of these functions is dynamic and requires constant surveillance 24/7 by a sensory system that feeds information to the CNS through afferent pathways and relays rapid responses through efferent pathways to the periphery. The brain can even be bypassed in reflexive responses. When you jerk your hand away from an open flame, your brain does not have to be involved in the immediate motor response but can leisurely consider what happened afterward. The ANS is also involved in disease either as a victim or as a culprit. We are now considering how to control the ANS in order to overcome symptoms and sometimes the causes of common diseases. These diseases alter the very functions listed above that are controlled by the ANS. For example, hypertension is an inappropriately high blood pressure at rest and/or during activity and may be brought on by dysfunction of the ANS favoring the sympathetic rather than the parasympathetic response (Mancia & Grassi, 2014). Strategies to rebalance this response include the use of drugs, meditation, and even direct neuronal stimulation using focused lasers (Colombo et al., 2021) in addition to major lifestyle changes to diet, activity, and ameliorating stresses (Schwalm et al., 2021). We know, probably from personal experience, that major lifestyle changes are difficult and take time. Therefore, the other measures to control the ANS are critical to explore to enhance efficacy and safety of novel therapies. The developing ANS can be vulnerable to a host of genetic and epigenetic influences because a large proportion of it develops from neural crest and placode derivatives. These multipotent cells develop early and are very active in proliferating, migrating, and differentiating and are sensitive to environmental information to guide their development. The authors of this special focus reveal how the ANS develops normally and what happens when it does not. They give us a taste of the vulnerability and central role of the ANS in our health and lead us to the conclusion that, in view of the gaps in our understanding of this ubiquitous system, much more research is warranted. The ANS could provide entry points for therapies to alleviate many chronic diseases. Drs. Sarah Schlatterer and Adre du Plessis in this issue provide an overview of how the ANS develops, how its functions can be measured, and reveal the range of factors that can significantly influence its development. These include “maternal mood and stress during and after pregnancy, fetal growth restriction, congenital heart disease, toxic exposures, and preterm birth” as well as maternal cigarette smoking and illicit drug use. The effects can emerge early or later in life and can manifest as cardiovascular or respiratory disease or neurodevelopmental and neuropsychiatric disorders. Drs. Altmirano and Wilson explain several developmental disorders of the ANS, apnea of prematurity, periodic breathing, sudden infant death syndrome (SIDS), and Rett syndrome that afflict neonates and young children. The complex cycles of sensing oxygen and CO2 levels and adjusting cardiorespiratory responses for proper gas exchange throughout the body is obviously crucial once outside the womb. Breathing rhythms are controlled for the most part autonomically and must be set up early on so that newborns can quickly transition to breathing air immediately after birth. Breathing disorders at this early stage lead to damage to many organs including the oxygen needy brain. The standard tests for autonomic function on adults (McGee, 2018), like tapping the knee with a rubber hammer, are unlikely to work on young infants and certainly not on fetuses. However, there is a non-invasive method that is being developed to sensitively assess ANS function by detailed analysis of the heartbeat. Dr. Luiz Fernando Martins de Souza Filho and colleagues explain that thanks to advanced technologies like Bluetooth, fetal, neonatal, and even premature infant heart rates can be sensitively detected and heart rate variability (HRV) analyzed. This approach is based on the measuring the fluctuating distance between the peaks of two consecutive R waves expressed in electrocardiograms (Shaffer & Ginsberg, 2017). These fluctuations are controlled by a Received: 21 April 2021 Accepted: 24 April 2021