Normative distribution of substance P and its tachykinin neurokinin-1 receptor in the medullary serotonergic network of the human infant during postnatal development

Substance P (SP) and its tachykinin NK1 receptor (NK1R) function within key medullary nuclei to regulate cardiorespiratory and autonomic control. We examined the normative distribution of SP and NK1R in the serotonergic (5-Hydroxytryptamine, [5-HT]) network of the human infant medulla during postnatal development, to provide a baseline to facilitate future analysis of the SP/NK1R system and its interaction with 5-HT within pediatric brainstem disorders in early life. [125I] labelled Bolton Hunter SP (BH-SP) tissue receptor autoradiography (n = 15), single label immunohistochemistry (IHC) and double label immunofluorescence (IF) (n = 10) were used to characterize the normative distribution profile of SP and NK1R in the 5-HT network of the human infant medulla during postnatal development. Tissue receptor autoradiography revealed extensive distribution of SP and NK1R in nuclei intimately related to cardiorespiratory function and autonomic control, with significant co-distribution and co-localization with 5-HT in the medullary network in the normal human infant during development. A trend for NK1R binding to decrease with age was observed with significantly higher binding in premature and male infants. We provide further evidence to suggest a significant role for SP/NK1R in the early postnatal period in the modulation of medullary cardiorespiratory and autonomic control in conjunction with medullary 5-HT mediated pathways and provide a baseline for future analysis of the potential consequences of abnormalities in these brainstem neurotransmitter networks during development.