Neonatal maternal separation and neuroendocrine programming of the respiratory control system in rats

Neonatal maternal separation (NMS) disrupts central nervous system (CNS) development. Although the consequences of NMS are typically linked with abnormal psychological and behavioural development, there is growing evidence indicating that NMS affects maturation of the respiratory control system. This review discusses results from animal studies in which ventilatory responses to chemical stimuli were measured either in unrestrained rats or in an anesthetised preparation. Data show that NMS interferes with development of ventilatory chemoreflexes in a persistent, sex-specific fashion by affecting both the central and peripheral components of the respiratory control system. NMS likely disrupts the balance between inhibitory (GABAergic) and excitatory modulation within key integrative structures involved in respiratory regulation. Because enhancement of ventilatory chemoreflexes is a hallmark of several cardio-respiratory disorders in humans these results raise important questions concerning the impact of the neonatal of environment on the emergence of respiratory disease related to neural control dysfunction later in life.