Unravelling the relationship between cigarette smoking and language development
Cigarette smoking (CS) is a leading cause of mortality and morbidity. Despite increasing knowledge regarding the health threats of CS, its global use remains a problem, even among pregnant women, with 8.1% of pregnant women smoking. In addition to maternal health, prenatal CS has been linked to neurodevelopmental disorders, such as ADHD and ASD, which include deficits in language skills. However, there is little research on CS specific effects on language skills. Nicotine, the addictive component of tobacco, exerts its cognitive effects by binding to the neuronal nicotinic acetylcholine choline receptors (nAChRs), among which the subtypes α7 and α4β2, have been linked to cognitive functions such as working memory (WM). Moreover, recent work linked a rare variant in Resistant to inhibitors of cholinesterase 3 (RIC3; NM_024557.4:c.262G>A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill with hypothesised association with exceptional WM capacity. Could RIC3 variants be a potential link between CS and offspring language outcomes via effects on nAChRs? First, using PubMed and Web Of Science, we systematically reviewed existing literature considering prenatal CS exposure and child language outcomes. Then, we compared the effects of RIC3A26S, RIC3V196FS, and RICT177S on the function of function of human α7 receptors using fluorescently tagged α7 nAChR and Forster's resonance energy transfer (FRET) microscopy imaging. Our systematic review reported negative effects of prenatal CS exposure on offspring language outcomes in 13 of 14 studies reviewed. Our apFRET experiments found the RIC3 variants studied introduced did not affect the interaction of RIC3 and α7 nAChRs in HEK cells. Conversely, in α4β2 experiments, introducing the V196F variant to RIC3 led to significantly increased α4 and β2 expression, as measured by fluorescence. The results of this study reinforce that prenatal CS exposure negatively impacts offspring language outcomes. None of the variants introduced to RIC3 increased interaction with α7, however, the significantly increased α4 and β2 expression in the presence of RICV196F, suggests that effects of RIC3 on language could lie in its effects on α4β2 expression.
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