Abstract
Abundant epidemiological data shows that maternal smoking during pregnancy or second-hand smoke exposure during neonatal life and infancy increases the incidence of respiratory illnesses later in life. However, underlying mechanisms initiated in early life but affecting adult disease remain undefined. Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are neurotrophic factors essential in promoting and maintaining differentiation, growth, and survival of central and peripheral nervous system. The goal of this proposal is to examine the potential role of neurotrophin release in mediating long-term effects of prenatal and early postnatal smoke exposure. Our studies showed that an initial exposure to smoke during prenatal and early postnatal periods significantly changed lung function, substance P (SP) innervation in trachea and the level of NGF in BAL fluid after re-exposure to smoke on adult (postnatal day (PD) 60). In controls, smoke exposure (PD 28) with a subsequent re-exposure at PD 60 did not affect lung function or SP innervation or NGF levels. PCR array revealed enhanced expression of multiple genes including NGF and its receptor by smoke exposure only during early prenatal periods. These data suggest that a critical period of exposure exists in early periods of development. Increased expression of NGF and its receptor in airway caused by smoke exposure may enhance susceptibility to respiratory illnesses in adult. These findings have obvious and significant implication both for smoking during pregnancy and the effects of second hand tobacco smoke exposure. The study provides evidence that prenatal and early postnatal life are periods of enhanced susceptibility to detrimental effects of cigarette smoke. These effects appear to be mediated through the release of neurotrophic factors like NGF which regulate growth and maturation of the airway during these susceptible periods.
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Wu, ZX., Kish, V., Batchelor, T. et al. Effects of Pre- and Post-natal smoke exposure on airway neural responses. Nat Prec (2007). https://doi.org/10.1038/npre.2007.1432.1
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DOI: https://doi.org/10.1038/npre.2007.1432.1