Examining the Emergence of Mood and Anxiety Molecular Phenotypes Resulting from Chronic Prenatal Nicotine Exposure in Cerebral Organoids
Abstract
Prenatal nicotine exposure (PNE) from maternal smoking disrupts regulatory processes vital to fetal development. These changes result in long-term behavioural impairments, including mood and anxiety disorders, that manifest later in life. However the relationship underlying PNE, and the underpinnings of mood/anxiety molecular phenotypes remains elusive. To model nicotine exposure during prenatal development, our study used human cerebral organoids that were chronically exposed to nicotine and collected for molecular analyses. Short-term, nicotine altered molecular markers of neural identity, mood/anxiety disorders and those involved in maintaining the excitatory/inhibitory (E/I) balance in the cortex. RNA sequencing further revealed transcriptomic changes in genes pertaining to embryonic development, neurogenesis, and DNA binding. Collectively, our results demonstrated that nicotine altered E/I balance, dopamine receptor expression and changes in neural identity markers that persist into later stages of development. These findings validate an in vitro model of PNE to better comprehend the emergence of neuropsychiatric molecular phenotypes resulting from gestational nicotine exposure.