Nicotine and brain development

Abstract

Preclinical studies, using primarily rodent models, have shown acetylcholine to have a critical role in brain maturation via activation of nicotinic acetylcholine receptors (nAChRs), a structurally diverse family of ligand-gated ion channels. nAChRs are widely expressed in fetal central nervous system, with transient upregulation in numerous brain regions during critical developmental periods. Activation of nAChRs can have varied developmental influences that are dependent on the pharmacologic properties and localization of the receptor. These include regulation of transmitter release, gene expression, neurite outgrowth, cell survival, and synapse formation and maturation. Aberrant exposure of fetal and neonatal brain to nicotine, through maternal smoking or nicotine replacement therapy (NRT), has been shown to have detrimental effects on cholinergic modulation of brain development. These include alterations in sexual differentiation of the brain, and in cell survival and synaptogenesis. Long-term alterations in the functional status and pharmacologic properties of nAChRs may also occur, which result in modifications of specific neural circuitry such as the brainstem cardiorespiratory network and sensory thalamocortical gating. Such alterations in brain structure and function may contribute to clinically characterized deficits that result from maternal smoking, such as sudden infant death syndrome and auditory-cognitive dysfunction. Although not the only constituent of tobacco smoke, there is now abundant evidence that nicotine is a neural teratogen. Thus, alternatives to NRT should be sought as tobacco cessation treatments in pregnant women.

Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

“…In a recent study, PNE was reported to reduce the cingulate cortex volume in mice (Zhu et al, 2012), as observed in AD/HD subjects (Makris et al, 2010), implying that the reduced thickness of cortical layers may be associated with the decrease in cell number induced by PNE. In addition, previous studies have demonstrated that nAChRs including α4β2 and α7 are expressed in progenitor cells in embryonic mouse brain (Dwyer et al, 2008). These studies support our present findings that α7 nAChRs mediate the decreased proliferation of neuronal progenitors by PNE in the VZ and SVZ layers on E14 (Figure 2 and Supplementary Figure S1).…”

“…In the developing brain, nAChRs have been implicated in neuronal proliferation, apoptosis, migration, and differentiation (Dwyer et al, 2008(Dwyer et al, , 2009. Accordingly, nicotine is likely to affect these processes during neurodevelopment, depending on the dose, developmental stage, and tissue or cell type.…”

“…The most abundant nAChR subtype is the α4β2 heteromer in the brain, a homomeric α7 assembly being the other major subtype. Overstimulation of nAChRs by nicotine may have varied developmental influences that are dependent on the pharmacologic properties and localization of the receptors (Dwyer et al, 2008).…”

Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

“…One explanation is that prenatal tobacco exposure directly affects brain development through nicotine, which has been demonstrated in animal studies (Dwyer et al, 2008). For example, a thinner somatosensory cortex in rats has been demonstrated (Roy and Sabherwal, 1994).…”

Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane

“…24 The a3b4 subtype is predominantly peripheral, but is also found in adult rat hippocampus 25 where it contributes to nicotine-evoked NE release from rat hippocampal synaptosomes. 26 27 The a4b2 and a3b4 nAChR subtypes selectively gate Na þ , whereas a7 nAChRs have a higher ratio of Ca 2þ to Na þ permeability.…”